Reprints, Supporting Info, Code: requests via email, or check below (see also Research Gate).
@article{Spelat2022,
author = {Spelat, Renza and Jihua, Nie and S{\'a}nchez Trivi{\~n}o, Cesar Adolfo and Pifferi, Simone and Pozzi, Diletta and Manzati, Matteo and Mortal, Simone and Schiavo, Irene and Spada, Federica and Zanchetta, Melania Eva and Ius, Tamara and Manini, Ivana and Rolle, Irene Giulia and Parisse, Pietro and Mill{\'a}n, Ana P and Bianconi, Ginestra and Cesca, Fabrizia and Giugliano, Michele and Menini, Anna and Cesselli, Daniela and Skrap, Miran and Torre, Vincent},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1038/s41419-022-05144-6},
journal = {Cell Death Dis},
journal-full = {Cell death \& disease},
mesh = {Brain Neoplasms; Exosomes; Glioma; Humans; Neurons; Quality of Life; Seizures; Tumor Microenvironment},
month = aug,
number = {8},
pages = {705},
pmc = {PMC9376103},
pmid = {35963860},
pst = {epublish},
title = {The dual action of glioma-derived exosomes on neuronal activity: synchronization and disruption of synchrony},
volume = {13},
year = {2022},
bdsk-url-1 = {https://doi.org/10.1038/s41419-022-05144-6}
}
Seizures represent a frequent symptom in gliomas and significantly impact patient morbidity and quality of life. Although the pathogenesis of tumor-related seizures is not fully understood, accumulating evidence indicates a key role of the peritumoral microenvironment. Brain cancer cells interact with neurons by forming synapses with them and by releasing exosomes, cytokines, and other small molecules. Strong interactions among neurons often lead to the synchronization of their activity. In this paper, we used an in vitro model to investigate the role of exosomes released by glioma cell lines and by patient-derived glioma stem cells (GSCs). The addition of exosomes released by U87 glioma cells to neuronal cultures at day in vitro (DIV) 4, when neurons are not yet synchronous, induces synchronization. At DIV 7-12 neurons become highly synchronous, and the addition of the same exosomes disrupts synchrony. By combining Ca2+ imaging, electrical recordings from single neurons with patch-clamp electrodes, substrate-integrated microelectrode arrays, and immunohistochemistry, we show that synchronization and de-synchronization are caused by the combined effect of (i) the formation of new neuronal branches, associated with a higher expression of Arp3, (ii) the modification of synaptic efficiency, and (iii) a direct action of exosomes on the electrical properties of neurons, more evident at DIV 7-12 when the threshold for spike initiation is significantly reduced. At DIV 7-12 exosomes also selectively boost glutamatergic signaling by increasing the number of excitatory synapses. Remarkably, de-synchronization was also observed with exosomes released by glioma-associated stem cells (GASCs) from patients with low-grade glioma but not from patients with high-grade glioma, where a more variable outcome was observed. These results show that exosomes released from glioma modify the electrical properties of neuronal networks and that de-synchronization caused by exosomes from low-grade glioma can contribute to the neurological pathologies of patients with brain cancers.
@article{Frisari2022,
author = {Frisari, Simone and Santo, Manuela and Hosseini, Ali and Manzati, Matteo and Giugliano, Michele and Mallamaci, Antonello},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3390/ijms23031343},
journal = {Int J Mol Sci},
journal-full = {International journal of molecular sciences},
keywords = {FOXG1 syndrome; functional gene profiling; multidimensional gene profiling; neural fate choice; neural progenitor proliferation; neuron activity; neuron morphology; precision therapy},
mesh = {Alleles; Animals; Brain; Cerebral Cortex; Forkhead Transcription Factors; Gene Expression; Gene Expression Regulation, Developmental; Gene Frequency; Humans; Mice; Nerve Tissue Proteins; Neurodevelopmental Disorders; Neurogenesis; Neurons; Primary Cell Culture; Proof of Concept Study},
month = jan,
number = {3},
pmc = {PMC8835715},
pmid = {35163265},
pst = {epublish},
title = {Multidimensional Functional Profiling of Human Neuropathogenic FOXG1 Alleles in Primary Cultures of Murine Pallial Precursors},
volume = {23},
year = {2022},
bdsk-url-1 = {https://doi.org/10.3390/ijms23031343}
}
FOXG1 is an ancient transcription factor gene mastering telencephalic development. A number of distinct structural FOXG1 mutations lead to the "FOXG1 syndrome", a complex and heterogeneous neuropathological entity, for which no cure is presently available. Reconstruction of primary neurodevelopmental/physiological anomalies evoked by these mutations is an obvious pre-requisite for future, precision therapy of such syndrome. Here, as a proof-of-principle, we functionally scored three FOXG1 neuropathogenic alleles, FOXG1G224S, FOXG1W308X, and FOXG1N232S, against their healthy counterpart. Specifically, we delivered transgenes encoding for them to dedicated preparations of murine pallial precursors and quantified their impact on selected neurodevelopmental and physiological processes mastered by Foxg1: pallial stem cell fate choice, proliferation of neural committed progenitors, neuronal architecture, neuronal activity, and their molecular correlates. Briefly, we found that FOXG1G224S and FOXG1W308X generally performed as a gain- and a loss-of-function-allele, respectively, while FOXG1N232S acted as a mild loss-of-function-allele or phenocopied FOXG1WT. These results provide valuable hints about processes misregulated in patients heterozygous for these mutations, to be re-addressed more stringently in patient iPSC-derivative neuro-organoids. Moreover, they suggest that murine pallial cultures may be employed for fast multidimensional profiling of novel, human neuropathogenic FOXG1 alleles, namely a step propedeutic to timely delivery of therapeutic precision treatments.
@article{Gandolfi2022,
author = {Gandolfi, Daniela and Puglisi, Francesco Maria and Serb, Alexander and Giugliano, Michele and Mapelli, Jonathan},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3389/fncel.2022.1115395},
journal = {Front Cell Neurosci},
journal-full = {Frontiers in cellular neuroscience},
keywords = {bio-inspired artificial intelligence; computational neuroscience; electronic; neuro-inspired computing; neuromorphic},
pages = {1115395},
pmc = {PMC9808067},
pmid = {36605614},
pst = {epublish},
title = {Editorial: Brain-inspired computing: Neuroscience drives the development of new electronics and artificial intelligence},
volume = {16},
year = {2022},
bdsk-url-1 = {https://doi.org/10.3389/fncel.2022.1115395}
}
@article{George2020,
author = {George, Richard and Chiappalone, Michela and Giugliano, Michele and Levi, Timoth{\'e}e and Vassanelli, Stefano and Partzsch, Johannes and Mayr, Christian},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1016/j.isci.2020.101589},
journal = {iScience},
journal-full = {iScience},
keywords = {Bioengineering; Computer Hardware; Computing Methodology; Neuroscience},
month = oct,
number = {10},
pages = {101589},
pmc = {PMC7554028},
pmid = {33083749},
pst = {epublish},
title = {Plasticity and Adaptation in Neuromorphic Biohybrid Systems},
volume = {23},
year = {2020},
bdsk-url-1 = {https://doi.org/10.1016/j.isci.2020.101589}
}
Neuromorphic systems take inspiration from the principles of biological information processing to form hardware platforms that enable the large-scale implementation of neural networks. The recent years have seen both advances in the theoretical aspects of spiking neural networks for their use in classification and control tasks and a progress in electrophysiological methods that is pushing the frontiers of intelligent neural interfacing and signal processing technologies. At the forefront of these new technologies, artificial and biological neural networks are tightly coupled, offering a novel "biohybrid" experimental framework for engineers and neurophysiologists. Indeed, biohybrid systems can constitute a new class of neuroprostheses opening important perspectives in the treatment of neurological disorders. Moreover, the use of biologically plausible learning rules allows forming an overall fault-tolerant system of co-developing subsystems. To identify opportunities and challenges in neuromorphic biohybrid systems, we discuss the field from the perspectives of neurobiology, computational neuroscience, and neuromorphic engineering.
@article{Verbist2020,
author = {Verbist, Christophe and M{\"u}ller, Michael G and Mansvelder, Huibert D and Legenstein, Robert and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1371/journal.pcbi.1008087},
journal = {PLoS Comput Biol},
journal-full = {PLoS computational biology},
mesh = {Action Potentials; Algorithms; Animals; Axon Initial Segment; Axons; Cerebral Cortex; Computational Biology; Computer Simulation; Dendrites; Humans; Imaging, Three-Dimensional; Linear Models; Machine Learning; Models, Neurological; Neocortex; Neurons; Potassium Channels; Rats},
month = jul,
number = {7},
pages = {e1008087},
pmc = {PMC7402515},
pmid = {32701953},
pst = {epublish},
title = {The location of the axon initial segment affects the bandwidth of spike initiation dynamics},
volume = {16},
year = {2020},
bdsk-url-1 = {https://doi.org/10.1371/journal.pcbi.1008087}
}
The dynamics and the sharp onset of action potential (AP) generation have recently been the subject of intense experimental and theoretical investigations. According to the resistive coupling theory, an electrotonic interplay between the site of AP initiation in the axon and the somato-dendritic load determines the AP waveform. This phenomenon not only alters the shape of APs recorded at the soma, but also determines the dynamics of excitability across a variety of time scales. Supporting this statement, here we generalize a previous numerical study and extend it to the quantification of the input-output gain of the neuronal dynamical response. We consider three classes of multicompartmental mathematical models, ranging from ball-and-stick simplified descriptions of neuronal excitability to 3D-reconstructed biophysical models of excitatory neurons of rodent and human cortical tissue. For each model, we demonstrate that increasing the distance between the axonal site of AP initiation and the soma markedly increases the bandwidth of neuronal response properties. We finally consider the Liquid State Machine paradigm, exploring the impact of altering the site of AP initiation at the level of a neuronal population, and demonstrate that an optimal distance exists to boost the computational performance of the network in a simple classification task.
@article{Manzati2020,
author = {Manzati, Matteo and Sorbo, Teresa and Giugliano, Michele and Ballerini, Laura},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1186/s13041-020-00619-z},
journal = {Mol Brain},
journal-full = {Molecular brain},
keywords = {Cell electrophysiology; Hippocampus; Microelectrode arrays; Neuronal networks; Neuronal progenitor cells},
mesh = {Action Potentials; Animals; Cells, Cultured; Coculture Techniques; Electrophysiological Phenomena; Hippocampus; Nerve Net; Neurogenesis; Neurons; Patch-Clamp Techniques; Rats; Rats, Wistar; Single-Cell Analysis},
month = may,
number = {1},
pages = {78},
pmc = {PMC7236481},
pmid = {32430072},
pst = {epublish},
title = {Foetal neural progenitors contribute to postnatal circuits formation ex vivo: an electrophysiological investigation},
volume = {13},
year = {2020},
bdsk-url-1 = {https://doi.org/10.1186/s13041-020-00619-z}
}
Neuronal progenitor cells (NPC) play an essential role in homeostasis of the central nervous system (CNS). Considering their ability to differentiate into specific lineages, their manipulation and control could have a major therapeutic impact for those CNS injuries or degenerative diseases characterized by neuronal cell loss. In this work, we established an in vitro co-culture and tested the ability of foetal NPC (fNPC) to integrate among post-mitotic hippocampal neurons and contribute to the electrical activity of the resulting networks. We performed extracellular electrophysiological recordings of the activity of neuronal networks and compared the properties of spontaneous spiking in hippocampal control cultures (HCC), fNPC, and mixed circuitries ex vivo. We further employed patch-clamp intracellular recordings to examine single-cell excitability. We report of the capability of fNPC to mature when combined to hippocampal neurons, shaping the profile of network activity, a result suggestive of newly formed connectivity ex vivo.
@article{Moskalyuk2020,
author = {Moskalyuk, Anastasiya and Van De Vijver, Sebastiaan and Verstraelen, Peter and De Vos, Winnok H and Kooy, R Frank and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1093/cercor/bhz068},
journal = {Cereb Cortex},
journal-full = {Cerebral cortex (New York, N.Y. : 1991)},
keywords = {fragile X; microelectrode arrays; network bursts; patch-clamp; spontaneous activity},
mesh = {Animals; Cerebral Cortex; Female; Fragile X Mental Retardation Protein; Fragile X Syndrome; Male; Mice, Inbred C57BL; Mice, Knockout; Models, Neurological; Neural Networks, Computer; Neural Pathways; Neurons},
month = jan,
number = {1},
pages = {31-46},
pmid = {30958540},
pst = {ppublish},
title = {Single-Cell and Neuronal Network Alterations in an In Vitro Model of Fragile X Syndrome},
volume = {30},
year = {2020},
bdsk-url-1 = {https://doi.org/10.1093/cercor/bhz068}
}
The Fragile X mental retardation protein (FMRP) is involved in many cellular processes and it regulates synaptic and network development in neurons. Its absence is known to lead to intellectual disability, with a wide range of comorbidities including autism. Over the past decades, FMRP research focused on abnormalities both in glutamatergic and GABAergic signaling, and an altered balance between excitation and inhibition has been hypothesized to underlie the clinical consequences of absence of the protein. Using Fmrp knockout mice, we studied an in vitro model of cortical microcircuitry and observed that the loss of FMRP largely affected the electrophysiological correlates of network development and maturation but caused less alterations in single-cell phenotypes. The loss of FMRP also caused a structural increase in the number of excitatory synaptic terminals. Using a mathematical model, we demonstrated that the combination of an increased excitation and reduced inhibition describes best our experimental observations during the ex vivo formation of the network connections.
@article{Lourenco2020,
author = {Louren{\c c}o, Joana and De Stasi, Angela Michela and Deleuze, Charlotte and Bigot, Mathilde and Pazienti, Antonio and Aguirre, Andrea and Giugliano, Michele and Ostojic, Srdjan and Bacci, Alberto},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1016/j.celrep.2019.12.052},
journal = {Cell Rep},
journal-full = {Cell reports},
keywords = {E/I ratio; GABAergic plasticity; PV cells; feedforward inhibition; gamma oscillations; layer 5; neocortex},
mesh = {Action Potentials; Animals; Female; Gamma Rhythm; Light; Long-Term Potentiation; Mice, Inbred C57BL; Models, Neurological; Neocortex; Neural Inhibition; Neuronal Plasticity; Pyramidal Cells; Synapses; Time Factors; gamma-Aminobutyric Acid},
month = jan,
number = {3},
pages = {630-641.e5},
pmc = {PMC6988114},
pmid = {31968242},
pst = {ppublish},
title = {Modulation of Coordinated Activity across Cortical Layers by Plasticity of Inhibitory Synapses},
volume = {30},
year = {2020},
bdsk-url-1 = {https://doi.org/10.1016/j.celrep.2019.12.052}
}
In the neocortex, synaptic inhibition shapes all forms of spontaneous and sensory evoked activity. Importantly, inhibitory transmission is highly plastic, but the functional role of inhibitory synaptic plasticity is unknown. In the mouse barrel cortex, activation of layer (L) 2/3 pyramidal neurons (PNs) elicits strong feedforward inhibition (FFI) onto L5 PNs. We find that FFI involving parvalbumin (PV)-expressing cells is strongly potentiated by postsynaptic PN burst firing. FFI plasticity modifies the PN excitation-to-inhibition (E/I) ratio, strongly modulates PN gain, and alters information transfer across cortical layers. Moreover, our LTPi-inducing protocol modifies firing of L5 PNs and alters the temporal association of PN spikes to γ-oscillations both in vitro and in vivo. All of these effects are captured by unbalancing the E/I ratio in a feedforward inhibition circuit model. Altogether, our results indicate that activity-dependent modulation of perisomatic inhibitory strength effectively influences the participation of single principal cortical neurons to cognition-relevant network activity.
@article{Borda-Bossana2020,
author = {Borda Bossana, Stefano and Verbist, Christophe and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3389/fncel.2020.00118},
journal = {Front Cell Neurosci},
journal-full = {Frontiers in cellular neuroscience},
keywords = {dynamical transfer function; interneuron; layer 1 cortex; noise; spike-triggered average},
pages = {118},
pmc = {PMC7313227},
pmid = {32625063},
pst = {epublish},
title = {Homogeneous and Narrow Bandwidth of Spike Initiation in Rat L1 Cortical Interneurons},
volume = {14},
year = {2020},
bdsk-url-1 = {https://doi.org/10.3389/fncel.2020.00118}
}
The cortical layer 1 (L1) contains a population of GABAergic interneurons, considered a key component of information integration, processing, and relaying in neocortical networks. In fact, L1 interneurons combine top-down information with feed-forward sensory inputs in layer 2/3 and 5 pyramidal cells (PCs), while filtering their incoming signals. Despite the importance of L1 for network emerging phenomena, little is known on the dynamics of the spike initiation and the encoding properties of its neurons. Using acute brain tissue slices from the rat neocortex, combined with the analysis of an existing database of model neurons, we investigated the dynamical transfer properties of these cells by sampling an entire population of known "electrical classes" and comparing experiments and model predictions. We found the bandwidth of spike initiation to be significantly narrower than in L2/3 and 5 PCs, with values below 100 cycle/s, but without significant heterogeneity in the cell response properties across distinct electrical types. The upper limit of the neuronal bandwidth was significantly correlated to the mean firing rate, as anticipated from theoretical studies but not reported for PCs. At high spectral frequencies, the magnitude of the neuronal response attenuated as a power-law, with an exponent significantly smaller than what was reported for pyramidal neurons and reminiscent of the dynamics of a "leaky" integrate-and-fire model of spike initiation. Finally, most of our in vitro results matched quantitatively the numerical simulations of the models as a further contribution to independently validate the models against novel experimental data.
@article{Jones2020,
author = {Jones, Peter D and Moskalyuk, Anastasiya and Barthold, Clemens and Gut{\"o}hrlein, Katja and Heusel, Gerhard and Schr{\"o}ppel, Birgit and Samba, Ramona and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3389/fnins.2020.00405},
journal = {Front Neurosci},
journal-full = {Frontiers in neuroscience},
keywords = {MEA; PEDOT; electrodeposition; neurotechnology; ultramicroelectrodes},
pages = {405},
pmc = {PMC7248397},
pmid = {32508562},
pst = {epublish},
title = {Low-Impedance 3D PEDOT:PSS Ultramicroelectrodes},
volume = {14},
year = {2020},
bdsk-url-1 = {https://doi.org/10.3389/fnins.2020.00405}
}
The technology for producing microelectrode arrays (MEAs) has been developing since the 1970s and extracellular electrophysiological recordings have become well established in neuroscience, drug screening and cardiology. MEAs allow monitoring of long-term spiking activity of large ensembles of excitable cells noninvasively with high temporal resolution and mapping its spatial features. However, their inability to register subthreshold potentials, such as intrinsic membrane oscillations and synaptic potentials, has inspired a number of laboratories to search for alternatives to bypass the restrictions and/or increase the sensitivity of microelectrodes. In this study, we present the fabrication and in vitro experimental validation of arrays of PEDOT:PSS-coated 3D ultramicroelectrodes, with the best-reported combination of small size and low electrochemical impedance. We observed that this type of microelectrode does not alter neuronal network biological properties, improves the signal quality of extracellular recordings and exhibits higher selectivity toward single unit recordings. With fabrication processes simpler than those reported in the literature for similar electrodes, our technology is a promising tool for study of neuronal networks.
@article{Linaro2019,
author = {Linaro, Daniele and Ocker, Gabriel K and Doiron, Brent and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1523/JNEUROSCI.3169-18.2019},
journal = {J Neurosci},
journal-full = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
keywords = {cortical interneurons; dynamic clamp; neocortex; noise correlations; pyramidal cells},
mesh = {Animals; Female; In Vitro Techniques; Interneurons; Male; Models, Neurological; Neocortex; Pyramidal Cells; Rats},
month = sep,
number = {39},
pages = {7648-7663},
pmc = {PMC6764207},
pmid = {31346031},
pst = {ppublish},
title = {Correlation Transfer by Layer 5 Cortical Neurons Under Recreated Synaptic Inputs In Vitro},
volume = {39},
year = {2019},
bdsk-url-1 = {https://doi.org/10.1523/JNEUROSCI.3169-18.2019}
}
Correlated electrical activity in neurons is a prominent characteristic of cortical microcircuits. Despite a growing amount of evidence concerning both spike-count and subthreshold membrane potential pairwise correlations, little is known about how different types of cortical neurons convert correlated inputs into correlated outputs. We studied pyramidal neurons and two classes of GABAergic interneurons of layer 5 in neocortical brain slices obtained from rats of both sexes, and we stimulated them with biophysically realistic correlated inputs, generated using dynamic clamp. We found that the physiological differences between cell types manifested unique features in their capacity to transfer correlated inputs. We used linear response theory and computational modeling to gain clear insights into how cellular properties determine both the gain and timescale of correlation transfer, thus tying single-cell features with network interactions. Our results provide further ground for the functionally distinct roles played by various types of neuronal cells in the cortical microcircuit.SIGNIFICANCE STATEMENT No matter how we probe the brain, we find correlated neuronal activity over a variety of spatial and temporal scales. For the cerebral cortex, significant evidence has accumulated on trial-to-trial covariability in synaptic inputs activation, subthreshold membrane potential fluctuations, and output spike trains. Although we do not yet fully understand their origin and whether they are detrimental or beneficial for information processing, we believe that clarifying how correlations emerge is pivotal for understanding large-scale neuronal network dynamics and computation. Here, we report quantitative differences between excitatory and inhibitory cells, as they relay input correlations into output correlations. We explain this heterogeneity by simple biophysical models and provide the most experimentally validated test of a theory for the emergence of correlations.
@article{Van-De-Vijver2019,
author = {Van De Vijver, Sebastiaan and Missault, Stephan and Van Soom, Jeroen and Van Der Veken, Pieter and Augustyns, Koen and Joossens, Jurgen and Dedeurwaerdere, Stefanie and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.7717/peerj.6796},
journal = {PeerJ},
journal-full = {PeerJ},
keywords = {Cortex; Electrophysiology; Extracellular matrix; Microelectrode arrays; Network activity; Neurobiology; Neurons; Patch-clamp; Serine proteases; Synaptic connectivity},
pages = {e6796},
pmc = {PMC6485206},
pmid = {31065460},
pst = {epublish},
title = {The effect of pharmacological inhibition of Serine Proteases on neuronal networks in vitro},
volume = {7},
year = {2019},
bdsk-url-1 = {https://doi.org/10.7717/peerj.6796}
}
Neurons are embedded in an extracellular matrix (ECM), which functions both as a scaffold and as a regulator of neuronal function. The ECM is in turn dynamically altered through the action of serine proteases, which break down its constituents. This pathway has been implicated in the regulation of synaptic plasticity and of neuronal intrinsic excitability. In this study, we determined the short-term effects of interfering with proteolytic processes in the ECM, with a newly developed serine protease inhibitor. We monitored the spontaneous electrophysiological activity of in vitro primary rat cortical cultures, using microelectrode arrays. While pharmacological inhibition at a low dosage had no significant effect, at elevated concentrations it altered significantly network synchronization and functional connectivity but left unaltered single-cell electrical properties. These results suggest that serine protease inhibition affects synaptic properties, likely through its actions on the ECM.
@article{Goriounova2018,
author = {Goriounova, Natalia A and Heyer, Djai B and Wilbers, Ren{\'e} and Verhoog, Matthijs B and Giugliano, Michele and Verbist, Christophe and Obermayer, Joshua and Kerkhofs, Amber and Smeding, Harri{\"e}t and Verberne, Maaike and Idema, Sander and Baayen, Johannes C and Pieneman, Anton W and de Kock, Christiaan Pj and Klein, Martin and Mansvelder, Huibert D},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.7554/eLife.41714},
journal = {Elife},
journal-full = {eLife},
keywords = {action potentials; dendrites; human; human cortex; human neurons; intelligence; neuroscience; pyramidal cells},
mesh = {Action Potentials; Adolescent; Adult; Aged; Brain; Computer Simulation; Female; Humans; Intelligence; Intelligence Tests; Male; Middle Aged; Models, Neurological; Pyramidal Cells; Young Adult},
month = dec,
pmc = {PMC6363383},
pmid = {30561325},
pst = {epublish},
title = {Large and fast human pyramidal neurons associate with intelligence},
volume = {7},
year = {2018},
bdsk-url-1 = {https://doi.org/10.7554/eLife.41714}
}
It is generally assumed that human intelligence relies on efficient processing by neurons in our brain. Although grey matter thickness and activity of temporal and frontal cortical areas correlate with IQ scores, no direct evidence exists that links structural and physiological properties of neurons to human intelligence. Here, we find that high IQ scores and large temporal cortical thickness associate with larger, more complex dendrites of human pyramidal neurons. We show in silico that larger dendritic trees enable pyramidal neurons to track activity of synaptic inputs with higher temporal precision, due to fast action potential kinetics. Indeed, we find that human pyramidal neurons of individuals with higher IQ scores sustain fast action potential kinetics during repeated firing. These findings provide the first evidence that human intelligence is associated with neuronal complexity, action potential kinetics and efficient information transfer from inputs to output within cortical neurons.
@article{Pampaloni2018a,
author = {Pampaloni, Niccol{\`o} Paolo and Lottner, Martin and Giugliano, Michele and Matruglio, Alessia and D'Amico, Francesco and Prato, Maurizio and Garrido, Jos{\`e} Antonio and Ballerini, Laura and Scaini, Denis},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1038/s41565-018-0163-6},
journal = {Nat Nanotechnol},
journal-full = {Nature nanotechnology},
mesh = {Action Potentials; Animals; Biocompatible Materials; Cell Communication; Cells, Cultured; Graphite; Nanostructures; Nerve Net; Neurons; Potassium; Rats},
month = aug,
number = {8},
pages = {755-764},
pmid = {29892019},
pst = {ppublish},
title = {Single-layer graphene modulates neuronal communication and augments membrane ion currents},
volume = {13},
year = {2018},
bdsk-url-1 = {https://doi.org/10.1038/s41565-018-0163-6}
}
The use of graphene-based materials to engineer sophisticated biosensing interfaces that can adapt to the central nervous system requires a detailed understanding of how such materials behave in a biological context. Graphene’s peculiar properties can cause various cellular changes, but the underlying mechanisms remain unclear. Here, we show that single-layer graphene increases neuronal firing by altering membrane-associated functions in cultured cells. Graphene tunes the distribution of extracellular ions at the interface with neurons, a key regulator of neuronal excitability. The resulting biophysical changes in the membrane include stronger potassium ion currents, with a shift in the fraction of neuronal firing phenotypes from adapting to tonically firing. By using experimental and theoretical approaches, we hypothesize that the graphene-ion interactions that are maximized when single-layer graphene is deposited on electrically insulating substrates are crucial to these effects.
@article{Espuny-Camacho2018,
author = {Espuny-Camacho, Ira and Michelsen, Kimmo A and Linaro, Daniele and Bilheu, Ang{\'e}line and Acosta-Verdugo, Sandra and Herpoel, Ad{\`e}le and Giugliano, Michele and Gaillard, Afsaneh and Vanderhaeghen, Pierre},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1016/j.celrep.2018.04.094},
journal = {Cell Rep},
journal-full = {Cell reports},
keywords = {brain repair; brain transplantation; cerebral cortex; neural wiring; pluripotent stem cells},
mesh = {Aging; Animals; Axons; Biomarkers; Cerebral Cortex; Human Embryonic Stem Cells; Humans; Mice, Inbred NOD; Mice, SCID; Neurons; Organ Specificity; Pluripotent Stem Cells; Synapses; Telencephalon; Visual Cortex},
month = may,
number = {9},
pages = {2732-2743},
pmc = {PMC5990494},
pmid = {29847802},
pst = {ppublish},
title = {Human Pluripotent Stem-Cell-Derived Cortical Neurons Integrate Functionally into the Lesioned Adult Murine Visual Cortex in an Area-Specific Way},
volume = {23},
year = {2018},
bdsk-url-1 = {https://doi.org/10.1016/j.celrep.2018.04.094}
}
The transplantation of pluripotent stem-cell-derived neurons constitutes a promising avenue for the treatment of several brain diseases. However, their potential for the repair of the cerebral cortex remains unclear, given its complexity and neuronal diversity. Here, we show that human visual cortical cells differentiated from embryonic stem cells can be transplanted and can integrate successfully into the lesioned mouse adult visual cortex. The transplanted human neurons expressed the appropriate repertoire of markers of six cortical layers, projected axons to specific visual cortical targets, and were synaptically active within the adult brain. Moreover, transplant maturation and integration were much less efficient following transplantation into the lesioned motor cortex, as previously observed for transplanted mouse cortical neurons. These data constitute an important milestone for the potential use of human PSC-derived cortical cells for the reassembly of cortical circuits and emphasize the importance of cortical areal identity for successful transplantation.
@article{Linaro2018,
author = {Linaro, Daniele and Bir{\'o}, Istv{\'a}n and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1111/ejn.13761},
journal = {Eur J Neurosci},
journal-full = {The European journal of neuroscience},
keywords = {dynamic-clamp; excitability; noise; patch clamping (electrophysiology); spike trains},
mesh = {Action Potentials; Animals; Female; Male; Neocortex; Pyramidal Cells; Rats; Rats, Wistar; Reaction Time; Synaptic Potentials},
month = jan,
number = {1},
pages = {17-32},
pmid = {29068098},
pst = {ppublish},
title = {Dynamical response properties of neocortical neurons to conductance-driven time-varying inputs},
volume = {47},
year = {2018},
bdsk-url-1 = {https://doi.org/10.1111/ejn.13761}
}
Ensembles of cortical neurons can track fast-varying inputs and relay them in their spike trains, far beyond the cut-off imposed by membrane passive electrical properties and mean firing rates. Initially explored in silico and later demonstrated experimentally, investigating how neurons respond to sinusoidally modulated stimuli provides a deeper insight into spike initiation mechanisms and information processing than conventional F-I curve methodologies. Besides net membrane currents, physiological synaptic inputs can also induce a stimulus-dependent modulation of the total membrane conductance, which is not reproduced by standard current-clamp protocols. Here, we investigated whether rat cortical neurons can track fast temporal modulations over a noisy conductance background. We also determined input-output transfer properties over a range of conditions, including: distinct presynaptic activation rates, postsynaptic firing rates and variability and type of temporal modulations. We found a very broad signal transfer bandwidth across all conditions, similar large cut-off frequencies and power-law attenuations of fast-varying inputs. At slow and intermediate input modulations, the response gain decreased for increasing output mean firing rates. The gain also decreased significantly for increasing intensities of background synaptic activity, thus generalising earlier studies on F-I curves. We also found a direct correlation between the action potentials’ onset rapidness and the neuronal bandwidth. Our novel results extend previous investigations of dynamical response properties to non-stationary and conductance-driven conditions, and provide computational neuroscientists with a novel set of observations that models must capture when aiming to replicate cortical cellular excitability.
@article{Pampaloni2018,
author = {Pampaloni, Niccol{\`o} Paolo and Giugliano, Michele and Scaini, Denis and Ballerini, Laura and Rauti, Rossana},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3389/fnins.2018.00953},
journal = {Front Neurosci},
journal-full = {Frontiers in neuroscience},
keywords = {nanomaterials; nanoscience; nanotools; neuroengineering; neuroscience},
pages = {953},
pmc = {PMC6341218},
pmid = {30697140},
pst = {epublish},
title = {Advances in Nano Neuroscience: From Nanomaterials to Nanotools},
volume = {12},
year = {2018},
bdsk-url-1 = {https://doi.org/10.3389/fnins.2018.00953}
}
During the last decades, neuroscientists have increasingly exploited a variety of artificial, de-novo synthesized materials with controlled nano-sized features. For instance, a renewed interest in the development of prostheses or neural interfaces was driven by the availability of novel nanomaterials that enabled the fabrication of implantable bioelectronics interfaces with reduced side effects and increased integration with the target biological tissue. The peculiar physical-chemical properties of nanomaterials have also contributed to the engineering of novel imaging devices toward sophisticated experimental settings, to smart fabricated scaffolds and microelectrodes, or other tools ultimately aimed at a better understanding of neural tissue functions. In this review, we focus on nanomaterials and specifically on carbon-based nanomaterials, such as carbon nanotubes (CNTs) and graphene. While these materials raise potential safety concerns, they represent a tremendous technological opportunity for the restoration of neuronal functions. We then describe nanotools such as nanowires and nano-modified MEA for high-performance electrophysiological recording and stimulation of neuronal electrical activity. We finally focus on the fabrication of three-dimensional synthetic nanostructures, used as substrates to interface biological cells and tissues in vitro and in vivo.
@article{Bifari2017,
author = {Bifari, Francesco and Decimo, Ilaria and Pino, Annachiara and Llorens-Bobadilla, Enric and Zhao, Sheng and Lange, Christian and Panuccio, Gabriella and Boeckx, Bram and Thienpont, Bernard and Vinckier, Stefan and Wyns, Sabine and Bouch{\'e}, Ann and Lambrechts, Diether and Giugliano, Michele and Dewerchin, Mieke and Martin-Villalba, Ana and Carmeliet, Peter},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1016/j.stem.2016.10.020},
journal = {Cell Stem Cell},
journal-full = {Cell stem cell},
keywords = {PDGFRβ; electrophysiology; lineage tracing; meninges; neonatal cerebral cortex; neural progenitors; neurogenesis; radial glia cells; single-cell RNA sequencing},
mesh = {Animals; Animals, Newborn; Cell Differentiation; Cell Lineage; Cell Movement; Cerebral Cortex; Embryo, Mammalian; Excitatory Amino Acid Transporter 1; Gene Expression Profiling; HEK293 Cells; Humans; Meninges; Mice, Inbred C57BL; Nestin; Neurogenesis; Neuroglia; Neurons; Receptor, Platelet-Derived Growth Factor beta; Reproducibility of Results; Single-Cell Analysis; Spheroids, Cellular; Staining and Labeling; Transcriptome},
month = mar,
number = {3},
pages = {360-373.e7},
pmid = {27889318},
pst = {ppublish},
title = {Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex},
volume = {20},
year = {2017},
bdsk-url-1 = {https://doi.org/10.1016/j.stem.2016.10.020}
}
Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2+ neurons in cortical layers II-IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex.
@article{Pulizzi2016,
author = {Pulizzi, Rocco and Musumeci, Gabriele and Van den Haute, Chris and Van De Vijver, Sebastiaan and Baekelandt, Veerle and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1038/srep24701},
journal = {Sci Rep},
journal-full = {Scientific reports},
mesh = {Animals; Cells, Cultured; Cerebral Cortex; Evoked Potentials; Gamma Rhythm; Gene Expression; In Vitro Techniques; Light; Models, Neurological; Neural Pathways; Neurons; Opsins; Photic Stimulation; Rats; Receptors, GABA-A; Synaptic Transmission},
month = apr,
pages = {24701},
pmc = {PMC4838830},
pmid = {27099182},
pst = {epublish},
title = {Brief wide-field photostimuli evoke and modulate oscillatory reverberating activity in cortical networks},
volume = {6},
year = {2016},
bdsk-url-1 = {https://doi.org/10.1038/srep24701}
}
Cell assemblies manipulation by optogenetics is pivotal to advance neuroscience and neuroengineering. In in vivo applications, photostimulation often broadly addresses a population of cells simultaneously, leading to feed-forward and to reverberating responses in recurrent microcircuits. The former arise from direct activation of targets downstream, and are straightforward to interpret. The latter are consequence of feedback connectivity and may reflect a variety of time-scales and complex dynamical properties. We investigated wide-field photostimulation in cortical networks in vitro, employing substrate-integrated microelectrode arrays and long-term cultured neuronal networks. We characterized the effect of brief light pulses, while restricting the expression of channelrhodopsin to principal neurons. We evoked robust reverberating responses, oscillating in the physiological gamma frequency range, and found that such a frequency could be reliably manipulated varying the light pulse duration, not its intensity. By pharmacology, mathematical modelling, and intracellular recordings, we conclude that gamma oscillations likely emerge as in vivo from the excitatory-inhibitory interplay and that, unexpectedly, the light stimuli transiently facilitate excitatory synaptic transmission. Of relevance for in vitro models of (dys)functional cortical microcircuitry and in vivo manipulations of cell assemblies, we give for the first time evidence of network-level consequences of the alteration of synaptic physiology by optogenetics.
@article{Segura2016,
author = {Segura, Inmaculada and Lange, Christian and Knevels, Ellen and Moskalyuk, Anastasiya and Pulizzi, Rocco and Eelen, Guy and Chaze, Thibault and Tudor, Cicerone and Boulegue, Cyril and Holt, Matthew and Daelemans, Dirk and Matondo, Mariette and Ghesqui{\`e}re, Bart and Giugliano, Michele and Ruiz de Almodovar, Carmen and Dewerchin, Mieke and Carmeliet, Peter},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1016/j.celrep.2016.02.047},
journal = {Cell Rep},
journal-full = {Cell reports},
mesh = {Amino Acids, Dicarboxylic; Animals; Cell Hypoxia; Cell Line, Tumor; Cells, Cultured; Dendritic Spines; Filamins; HEK293 Cells; Hippocampus; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; Mice; Mice, Knockout; Oxygen; Rats; Rats, Wistar; Synapses; Tubulin; Up-Regulation; Von Hippel-Lindau Tumor Suppressor Protein},
month = mar,
number = {11},
pages = {2653-67},
pmc = {PMC4805856},
pmid = {26972007},
pst = {ppublish},
title = {The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A},
volume = {14},
year = {2016},
bdsk-url-1 = {https://doi.org/10.1016/j.celrep.2016.02.047}
}
Neuronal function is highly sensitive to changes in oxygen levels, but how hypoxia affects dendritic spine formation and synaptogenesis is unknown. Here we report that hypoxia, chemical inhibition of the oxygen-sensing prolyl hydroxylase domain proteins (PHDs), and silencing of Phd2 induce immature filopodium-like dendritic protrusions, promote spine regression, reduce synaptic density, and decrease the frequency of spontaneous action potentials independently of HIF signaling. We identified the actin cross-linker filamin A (FLNA) as a target of PHD2 mediating these effects. In normoxia, PHD2 hydroxylates the proline residues P2309 and P2316 in FLNA, leading to von Hippel-Lindau (VHL)-mediated ubiquitination and proteasomal degradation. In hypoxia, PHD2 inactivation rapidly upregulates FLNA protein levels because of blockage of its proteasomal degradation. FLNA upregulation induces more immature spines, whereas Flna silencing rescues the immature spine phenotype induced by PHD2 inhibition.
@article{Peelaerts2015,
author = {Peelaerts, W and Bousset, L and Van der Perren, A and Moskalyuk, A and Pulizzi, R and Giugliano, M and Van den Haute, C and Melki, R and Baekelandt, V},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1038/nature14547},
journal = {Nature},
journal-full = {Nature},
mesh = {Animals; Blood-Brain Barrier; Brain; Female; Humans; Lewy Body Disease; Multiple System Atrophy; Parkinson Disease; Phenotype; Rats; Rats, Wistar; Substantia Nigra; Synapses; alpha-Synuclein},
month = jun,
number = {7556},
pages = {340-4},
pmid = {26061766},
pst = {ppublish},
title = {α-Synuclein strains cause distinct synucleinopathies after local and systemic administration},
volume = {522},
year = {2015},
bdsk-url-1 = {https://doi.org/10.1038/nature14547}
}
Misfolded protein aggregates represent a continuum with overlapping features in neurodegenerative diseases, but differences in protein components and affected brain regions. The molecular hallmark of synucleinopathies such as Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy are megadalton α-synuclein-rich deposits suggestive of one molecular event causing distinct disease phenotypes. Glial α-synuclein (α-SYN) filamentous deposits are prominent in multiple system atrophy and neuronal α-SYN inclusions are found in Parkinson’s disease and dementia with Lewy bodies. The discovery of α-SYN assemblies with different structural characteristics or ’strains’ has led to the hypothesis that strains could account for the different clinico-pathological traits within synucleinopathies. In this study we show that α-SYN strain conformation and seeding propensity lead to distinct histopathological and behavioural phenotypes. We assess the properties of structurally well-defined α-SYN assemblies (oligomers, ribbons and fibrils) after injection in rat brain. We prove that α-SYN strains amplify in vivo. Fibrils seem to be the major toxic strain, resulting in progressive motor impairment and cell death, whereas ribbons cause a distinct histopathological phenotype displaying Parkinson’s disease and multiple system atrophy traits. Additionally, we show that α-SYN assemblies cross the blood-brain barrier and distribute to the central nervous system after intravenous injection. Our results demonstrate that distinct α-SYN strains display differential seeding capacities, inducing strain-specific pathology and neurotoxic phenotypes.
@article{Linaro2015,
author = {Linaro, Daniele and Couto, Jo{\~a}o and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3791/52320},
journal = {J Vis Exp},
journal-full = {Journal of visualized experiments : JoVE},
mesh = {Animals; Electrophysiology; Neurons; Pyramidal Cells; Rats; Rats, Wistar},
month = jun,
number = {100},
pages = {e52320},
pmc = {PMC4545205},
pmid = {26132434},
pst = {epublish},
title = {Real-time Electrophysiology: Using Closed-loop Protocols to Probe Neuronal Dynamics and Beyond},
year = {2015},
bdsk-url-1 = {https://doi.org/10.3791/52320}
}
Experimental neuroscience is witnessing an increased interest in the development and application of novel and often complex, closed-loop protocols, where the stimulus applied depends in real-time on the response of the system. Recent applications range from the implementation of virtual reality systems for studying motor responses both in mice and in zebrafish, to control of seizures following cortical stroke using optogenetics. A key advantage of closed-loop techniques resides in the capability of probing higher dimensional properties that are not directly accessible or that depend on multiple variables, such as neuronal excitability and reliability, while at the same time maximizing the experimental throughput. In this contribution and in the context of cellular electrophysiology, we describe how to apply a variety of closed-loop protocols to the study of the response properties of pyramidal cortical neurons, recorded intracellularly with the patch clamp technique in acute brain slices from the somatosensory cortex of juvenile rats. As no commercially available or open source software provides all the features required for efficiently performing the experiments described here, a new software toolbox called LCG was developed, whose modular structure maximizes reuse of computer code and facilitates the implementation of novel experimental paradigms. Stimulation waveforms are specified using a compact meta-description and full experimental protocols are described in text-based configuration files. Additionally, LCG has a command-line interface that is suited for repetition of trials and automation of experimental protocols.
@article{Couto2015,
author = {Couto, Jo{\~a}o and Linaro, Daniele and De Schutter, E and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1371/journal.pcbi.1004112},
journal = {PLoS Comput Biol},
journal-full = {PLoS computational biology},
mesh = {Action Potentials; Animals; Computational Biology; Computer Simulation; Models, Neurological; Purkinje Cells; Rats; Rats, Wistar},
month = mar,
number = {3},
pages = {e1004112},
pmc = {PMC4361458},
pmid = {25775448},
pst = {epublish},
title = {On the firing rate dependency of the phase response curve of rat Purkinje neurons in vitro},
volume = {11},
year = {2015},
bdsk-url-1 = {https://doi.org/10.1371/journal.pcbi.1004112}
}
Synchronous spiking during cerebellar tasks has been observed across Purkinje cells: however, little is known about the intrinsic cellular mechanisms responsible for its initiation, cessation and stability. The Phase Response Curve (PRC), a simple input-output characterization of single cells, can provide insights into individual and collective properties of neurons and networks, by quantifying the impact of an infinitesimal depolarizing current pulse on the time of occurrence of subsequent action potentials, while a neuron is firing tonically. Recently, the PRC theory applied to cerebellar Purkinje cells revealed that these behave as phase-independent integrators at low firing rates, and switch to a phase-dependent mode at high rates. Given the implications for computation and information processing in the cerebellum and the possible role of synchrony in the communication with its post-synaptic targets, we further explored the firing rate dependency of the PRC in Purkinje cells. We isolated key factors for the experimental estimation of the PRC and developed a closed-loop approach to reliably compute the PRC across diverse firing rates in the same cell. Our results show unambiguously that the PRC of individual Purkinje cells is firing rate dependent and that it smoothly transitions from phase independent integrator to a phase dependent mode. Using computational models we show that neither channel noise nor a realistic cell morphology are responsible for the rate dependent shift in the phase response curve.
@article{Biro2015,
author = {Bir{\'o}, Istv{\'a}n and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3389/fninf.2015.00017},
journal = {Front Neuroinform},
journal-full = {Frontiers in neuroinformatics},
keywords = {active electrode compensation; cellular neurobiology; closed loop; dynamic clamp; electrophysiology; experimental control; extracellular stimulation; response clamp},
pages = {17},
pmc = {PMC4477165},
pmid = {26157385},
pst = {epublish},
title = {A reconfigurable visual-programming library for real-time closed-loop cellular electrophysiology},
volume = {9},
year = {2015},
bdsk-url-1 = {https://doi.org/10.3389/fninf.2015.00017}
}
Most of the software platforms for cellular electrophysiology are limited in terms of flexibility, hardware support, ease of use, or re-configuration and adaptation for non-expert users. Moreover, advanced experimental protocols requiring real-time closed-loop operation to investigate excitability, plasticity, dynamics, are largely inaccessible to users without moderate to substantial computer proficiency. Here we present an approach based on MATLAB/Simulink, exploiting the benefits of LEGO-like visual programming and configuration, combined to a small, but easily extendible library of functional software components. We provide and validate several examples, implementing conventional and more sophisticated experimental protocols such as dynamic-clamp or the combined use of intracellular and extracellular methods, involving closed-loop real-time control. The functionality of each of these examples is demonstrated with relevant experiments. These can be used as a starting point to create and support a larger variety of electrophysiological tools and methods, hopefully extending the range of default techniques and protocols currently employed in experimental labs across the world.
@article{Warnaar2015,
author = {Warnaar, Pascal and Couto, Joao and Negrello, Mario and Junker, Marc and Smilgin, Aleksandra and Ignashchenkova, Alla and Giugliano, Michele and Thier, Peter and De Schutter, Erik},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3389/fncel.2015.00122},
journal = {Front Cell Neurosci},
journal-full = {Frontiers in cellular neuroscience},
keywords = {Purkinje neuron; complex spike; monkey; saccades; waveform},
pages = {122},
pmc = {PMC4394703},
pmid = {25918500},
pst = {epublish},
title = {Duration of Purkinje cell complex spikes increases with their firing frequency},
volume = {9},
year = {2015},
bdsk-url-1 = {https://doi.org/10.3389/fncel.2015.00122}
}
Climbing fiber (CF) triggered complex spikes (CS) are massive depolarization bursts in the cerebellar Purkinje cell (PC), showing several high frequency spikelet components (\pm600 Hz). Since its early observations, the CS is known to vary in shape. In this study we describe CS waveforms, extracellularly recorded in awake primates (Macaca mulatta) performing saccades. Every PC analyzed showed a range of CS shapes with profoundly different duration and number of spikelets. The initial part of the CS was rather constant but the later part differed greatly, with a pronounced jitter of the last spikelets causing a large variation in total CS duration. Waveforms did not effect the following pause duration in the simple spike (SS) train, nor were SS firing rates predictive of the waveform shapes or vice versa. The waveforms did not differ between experimental conditions nor was there a preferred sequential order of CS shapes throughout the recordings. Instead, part of their variability, the timing jitter of the CS’s last spikelets, strongly correlated with interval length to the preceding CS: shorter CS intervals resulted in later appearance of the last spikelets in the CS burst, and vice versa. A similar phenomenon was observed in rat PCs recorded in vitro upon repeated extracellular stimulation of CFs at different frequencies in slice experiments. All together these results strongly suggest that the variability in the timing of the last spikelet is due to CS frequency dependent changes in PC excitability.
@article{Monaco2015,
author = {Monaco, Antonina M and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3762/bjnano.6.51},
journal = {Beilstein J Nanotechnol},
journal-full = {Beilstein journal of nanotechnology},
keywords = {carbon nanotubes; electrophysiology; graphene; microelectrodes; nanodiamonds; nanotechnology; neuroengineering; neuronal cultures; neuroscience},
pages = {499},
pmc = {PMC4361967},
pmid = {25821691},
pst = {epublish},
title = {Correction: Carbon-based smart nanomaterials in biomedicine and neuroengineering},
volume = {6},
year = {2015},
bdsk-url-1 = {https://doi.org/10.3762/bjnano.6.51}
}
[This corrects the article DOI: 10.3762/bjnano.5.196.].
@article{Gehring2015,
author = {Gehring, Tiago V and Vasilaki, Eleni and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1109/EMBC.2015.7319315},
journal = {Annu Int Conf IEEE Eng Med Biol Soc},
journal-full = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
mesh = {Animals; Electrodes; Electrophysiological Phenomena; Humans; Microarray Analysis; Signal Processing, Computer-Assisted; Software},
pages = {4178-81},
pmid = {26737215},
pst = {ppublish},
title = {Highly scalable parallel processing of extracellular recordings of Multielectrode Arrays},
volume = {2015},
year = {2015},
bdsk-url-1 = {https://doi.org/10.1109/EMBC.2015.7319315}
}
Technological advances of Multielectrode Arrays (MEAs) used for multisite, parallel electrophysiological recordings, lead to an ever increasing amount of raw data being generated. Arrays with hundreds up to a few thousands of electrodes are slowly seeing widespread use and the expectation is that more sophisticated arrays will become available in the near future. In order to process the large data volumes resulting from MEA recordings there is a pressing need for new software tools able to process many data channels in parallel. Here we present a new tool for processing MEA data recordings that makes use of new programming paradigms and recent technology developments to unleash the power of modern highly parallel hardware, such as multi-core CPUs with vector instruction sets or GPGPUs. Our tool builds on and complements existing MEA data analysis packages. It shows high scalability and can be used to speed up some performance critical pre-processing steps such as data filtering and spike detection, helping to make the analysis of larger data sets tractable.
@article{Testa-Silva2014,
author = {Testa-Silva, Guilherme and Verhoog, Matthijs B and Linaro, Daniele and de Kock, Christiaan P J and Baayen, Johannes C and Meredith, Rhiannon M and De Zeeuw, Chris I and Giugliano, Michele and Mansvelder, Huibert D},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1371/journal.pbio.1002007},
journal = {PLoS Biol},
journal-full = {PLoS biology},
mesh = {Adolescent; Adult; Animals; Humans; Mice, Inbred C57BL; Middle Aged; Neocortex; Pyramidal Cells; Synapses; Young Adult},
month = nov,
number = {11},
pages = {e1002007},
pmc = {PMC4244038},
pmid = {25422947},
pst = {epublish},
title = {High bandwidth synaptic communication and frequency tracking in human neocortex},
volume = {12},
year = {2014},
bdsk-url-1 = {https://doi.org/10.1371/journal.pbio.1002007}
}
Neuronal firing, synaptic transmission, and its plasticity form the building blocks for processing and storage of information in the brain. It is unknown whether adult human synapses are more efficient in transferring information between neurons than rodent synapses. To test this, we recorded from connected pairs of pyramidal neurons in acute brain slices of adult human and mouse temporal cortex and probed the dynamical properties of use-dependent plasticity. We found that human synaptic connections were purely depressing and that they recovered three to four times more swiftly from depression than synapses in rodent neocortex. Thereby, during realistic spike trains, the temporal resolution of synaptic information exchange in human synapses substantially surpasses that in mice. Using information theory, we calculate that information transfer between human pyramidal neurons exceeds that of mouse pyramidal neurons by four to nine times, well into the beta and gamma frequency range. In addition, we found that human principal cells tracked fine temporal features, conveyed in received synaptic inputs, at a wider bandwidth than for rodents. Action potential firing probability was reliably phase-locked to input transients up to 1,000 cycles/s because of a steep onset of action potentials in human pyramidal neurons during spike trains, unlike in rodent neurons. Our data show that, in contrast to the widely held views of limited information transfer in rodent depressing synapses, fast recovering synapses of human neurons can actually transfer substantial amounts of information during spike trains. In addition, human pyramidal neurons are equipped to encode high synaptic information content. Thus, adult human cortical microcircuits relay information at a wider bandwidth than rodent microcircuits.
@article{Curtis2014,
author = {Curtis, Daniel J and Sood, Aman and Phillips, Tom J and Leinster, Veronica H L and Nishiguchi, Akihiro and Coyle, Christopher and Lacharme-Lora, Lizeth and Beaumont, Oliver and Kemp, Helena and Goodall, Roberta and Cornes, Leila and Giugliano, Michele and Barone, Rocco A and Matsusaki, Michiya and Akashi, Mitsuru and Tanaka, Hiroyoshi Y and Kano, Mitsunobu and McGarvey, Jennifer and Halemani, Nagaraj D and Simon, Katja and Keehan, Robert and Ind, William and Masters, Tracey and Grant, Simon and Athwal, Sharan and Collett, Gavin and Tannetta, Dionne and Sargent, Ian L and Scull-Brown, Emma and Liu, Xun and Aquilina, Kristian and Cohen, Nicki and Lane, Jon D and Thoresen, Marianne and Hanley, Jon and Randall, Andrew and Case, C Patrick},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1016/j.expneurol.2014.05.003},
journal = {Exp Neurol},
journal-full = {Experimental neurology},
keywords = {Cerebral cortex; Dendrite; Development; Hypoxia; Neurodevelopmental disorder; Neurone; Parvalbumin; Placenta; Reoxygenation; Schizophrenia},
mesh = {Animals; Animals, Newborn; Brain; Cell Hypoxia; Cells, Cultured; Cerebral Cortex; Culture Media, Conditioned; Dendrites; Dose-Response Relationship, Drug; Embryo, Mammalian; Female; Fetus; Glial Fibrillary Acidic Protein; Humans; Hypoxia; Membrane Potentials; Neurons; Oxygen; Placenta; Pregnancy; Rats; Rats, Wistar; Reactive Oxygen Species; Tissue Culture Techniques},
month = nov,
pages = {386-95},
pmid = {24818543},
pst = {ppublish},
title = {Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions},
volume = {261},
year = {2014},
bdsk-url-1 = {https://doi.org/10.1016/j.expneurol.2014.05.003}
}
Some psychiatric diseases in children and young adults are thought to originate from adverse exposures during foetal life, including hypoxia and hypoxia/reoxygenation. The mechanism is not understood. Several authors have emphasised that the placenta is likely to play an important role as the key interface between mother and foetus. Here we have explored whether a first trimester human placenta or model barrier of primary human cytotrophoblasts might secrete factors, in response to hypoxia or hypoxia/reoxygenation, that could damage neurones. We find that the secretions in conditioned media caused an increase of [Ca(2+)]i and mitochondrial free radicals and a decrease of dendritic lengths, branching complexity, spine density and synaptic activity in dissociated neurones from embryonic rat cerebral cortex. There was altered staining of glutamate and GABA receptors. We identify glutamate as an active factor within the conditioned media and demonstrate a specific release of glutamate from the placenta/cytotrophoblast barriers invitro after hypoxia or hypoxia/reoxygenation. Injection of conditioned media into developing brains of P4 rats reduced the numerical density of parvalbumin-containing neurones in cortex, hippocampus and reticular nucleus, reduced immunostaining of glutamate receptors and altered cellular turnover. These results show that the placenta is able to release factors, in response to altered oxygen, that can damage developing neurones under experimental conditions.
@article{Linaro2014,
author = {Linaro, Daniele and Couto, Jo{\~a}o and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1016/j.jneumeth.2014.04.003},
journal = {J Neurosci Methods},
journal-full = {Journal of neuroscience methods},
keywords = {Active Electrode Compensation; Cellular neurobiology; Closed-loop; Command-line interface; Current clamp; Dynamic clamp; Electrophysiology; Experimental control; Hybrid experiments; Neuroinformatics; Real-time computing; Scripted electrophysiology},
mesh = {Action Potentials; Algorithms; Animals; Cerebellar Cortex; Computer Simulation; Electric Stimulation; Electrophysiology; Models, Neurological; Neurons; Patch-Clamp Techniques; Pyramidal Cells; Rats, Wistar; Signal Processing, Computer-Assisted; Software; Somatosensory Cortex; Time Factors; Tissue Culture Techniques; User-Computer Interface},
month = jun,
pages = {5-19},
pmid = {24769169},
pst = {ppublish},
title = {Command-line cellular electrophysiology for conventional and real-time closed-loop experiments},
volume = {230},
year = {2014},
bdsk-url-1 = {https://doi.org/10.1016/j.jneumeth.2014.04.003}
}
BACKGROUND: Current software tools for electrophysiological experiments are limited in flexibility and rarely offer adequate support for advanced techniques such as dynamic clamp and hybrid experiments, which are therefore limited to laboratories with a significant expertise in neuroinformatics. NEW METHOD: We have developed lcg, a software suite based on a command-line interface (CLI) that allows performing both standard and advanced electrophysiological experiments. Stimulation protocols for classical voltage and current clamp experiments are defined by a concise and flexible meta description that allows representing complex waveforms as a piece-wise parametric decomposition of elementary sub-waveforms, abstracting the stimulation hardware. To perform complex experiments lcg provides a set of elementary building blocks that can be interconnected to yield a large variety of experimental paradigms. RESULTS: We present various cellular electrophysiological experiments in which lcg has been employed, ranging from the automated application of current clamp protocols for characterizing basic electrophysiological properties of neurons, to dynamic clamp, response clamp, and hybrid experiments. We finally show how the scripting capabilities behind a CLI are suited for integrating experimental trials into complex workflows, where actual experiment, online data analysis and computational modeling seamlessly integrate. COMPARISON WITH EXISTING METHODS: We compare lcg with two open source toolboxes, RTXI and RELACS. CONCLUSIONS: We believe that lcg will greatly contribute to the standardization and reproducibility of both simple and complex experiments. Additionally, on the long run the increased efficiency due to a CLI will prove a great benefit for the experimental community.
@article{Reinartz2014,
author = {Reinartz, Sebastian and Biro, Istvan and Gal, Asaf and Giugliano, Michele and Marom, Shimon},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3389/fncir.2014.00071},
journal = {Front Neural Circuits},
journal-full = {Frontiers in neural circuits},
keywords = {cortical culture; cortical slice; electrical stimulation; microelectrode array; patch clamp; response fluctuations; single neuron; synaptic dynamics},
mesh = {Action Potentials; Animals; Animals, Newborn; Cells, Cultured; Cerebral Cortex; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; In Vitro Techniques; Long-Term Potentiation; Nerve Net; Neurons; Neurotransmitter Agents; Nonlinear Dynamics; Rats; Rats, Sprague-Dawley; Synapses; Synaptic Transmission},
pages = {71},
pmc = {PMC4077315},
pmid = {25071452},
pst = {epublish},
title = {Synaptic dynamics contribute to long-term single neuron response fluctuations},
volume = {8},
year = {2014},
bdsk-url-1 = {https://doi.org/10.3389/fncir.2014.00071}
}
Firing rate variability at the single neuron level is characterized by long-memory processes and complex statistics over a wide range of time scales (from milliseconds up to several hours). Here, we focus on the contribution of non-stationary efficacy of the ensemble of synapses-activated in response to a given stimulus-on single neuron response variability. We present and validate a method tailored for controlled and specific long-term activation of a single cortical neuron in vitro via synaptic or antidromic stimulation, enabling a clear separation between two determinants of neuronal response variability: membrane excitability dynamics vs. synaptic dynamics. Applying this method we show that, within the range of physiological activation frequencies, the synaptic ensemble of a given neuron is a key contributor to the neuronal response variability, long-memory processes and complex statistics observed over extended time scales. Synaptic transmission dynamics impact on response variability in stimulation rates that are substantially lower compared to stimulation rates that drive excitability resources to fluctuate. Implications to network embedded neurons are discussed.
@article{Esposito2014a,
author = {Esposito, Umberto and Giugliano, Michele and van Rossum, Mark and Vasilaki, Eleni},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1371/journal.pone.0100805},
journal = {PLoS One},
journal-full = {PloS one},
mesh = {Algorithms; Computer Simulation; Connectome; Humans; Models, Neurological; Nerve Net; Neuronal Plasticity; Stochastic Processes},
number = {7},
pages = {e100805},
pmc = {PMC4090069},
pmid = {25006663},
pst = {epublish},
title = {Measuring symmetry, asymmetry and randomness in neural network connectivity},
volume = {9},
year = {2014},
bdsk-url-1 = {https://doi.org/10.1371/journal.pone.0100805}
}
Cognitive functions are stored in the connectome, the wiring diagram of the brain, which exhibits non-random features, so-called motifs. In this work, we focus on bidirectional, symmetric motifs, i.e. two neurons that project to each other via connections of equal strength, and unidirectional, non-symmetric motifs, i.e. within a pair of neurons only one neuron projects to the other. We hypothesise that such motifs have been shaped via activity dependent synaptic plasticity processes. As a consequence, learning moves the distribution of the synaptic connections away from randomness. Our aim is to provide a global, macroscopic, single parameter characterisation of the statistical occurrence of bidirectional and unidirectional motifs. To this end we define a symmetry measure that does not require any a priori thresholding of the weights or knowledge of their maximal value. We calculate its mean and variance for random uniform or Gaussian distributions, which allows us to introduce a confidence measure of how significantly symmetric or asymmetric a specific configuration is, i.e. how likely it is that the configuration is the result of chance. We demonstrate the discriminatory power of our symmetry measure by inspecting the eigenvalues of different types of connectivity matrices. We show that a Gaussian weight distribution biases the connectivity motifs to more symmetric configurations than a uniform distribution and that introducing a random synaptic pruning, mimicking developmental regulation in synaptogenesis, biases the connectivity motifs to more asymmetric configurations, regardless of the distribution. We expect that our work will benefit the computational modelling community, by providing a systematic way to characterise symmetry and asymmetry in network structures. Further, our symmetry measure will be of use to electrophysiologists that investigate symmetry of network connectivity.
@article{Monaco2014,
author = {Monaco, Antonina M and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3762/bjnano.5.196},
journal = {Beilstein J Nanotechnol},
journal-full = {Beilstein journal of nanotechnology},
keywords = {carbon nanotubes; electrophysiology; graphene; microelectrodes; nanodiamonds; nanotechnology; neuroengineering; neuronal cultures; neuroscience},
pages = {1849-63},
pmc = {PMC4222354},
pmid = {25383297},
pst = {epublish},
title = {Carbon-based smart nanomaterials in biomedicine and neuroengineering},
volume = {5},
year = {2014},
bdsk-url-1 = {https://doi.org/10.3762/bjnano.5.196}
}
The search for advanced biomimetic materials that are capable of offering a scaffold for biological tissues during regeneration or of electrically connecting artificial devices with cellular structures to restore damaged brain functions is at the forefront of interdisciplinary research in materials science. Bioactive nanoparticles for drug delivery, substrates for nerve regeneration and active guidance, as well as supramolecular architectures mimicking the extracellular environment to reduce inflammatory responses in brain implants, are within reach thanks to the advancements in nanotechnology. In particular, carbon-based nanostructured materials, such as graphene, carbon nanotubes (CNTs) and nanodiamonds (NDs), have demonstrated to be highly promising materials for designing and fabricating nanoelectrodes and substrates for cell growth, by virtue of their peerless optical, electrical, thermal, and mechanical properties. In this review we discuss the state-of-the-art in the applications of nanomaterials in biological and biomedical fields, with a particular emphasis on neuroengineering.
@article{Esposito2014,
author = {Esposito, Umberto and Giugliano, Michele and Vasilaki, Eleni},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3389/fncom.2014.00175},
journal = {Front Comput Neurosci},
journal-full = {Frontiers in computational neuroscience},
keywords = {learning; long-term plasticity; motifs; rate code; short-term plasticity; target-specificity},
pages = {175},
pmc = {PMC4310301},
pmid = {25688203},
pst = {epublish},
title = {Adaptation of short-term plasticity parameters via error-driven learning may explain the correlation between activity-dependent synaptic properties, connectivity motifs and target specificity},
volume = {8},
year = {2014},
bdsk-url-1 = {https://doi.org/10.3389/fncom.2014.00175}
}
The anatomical connectivity among neurons has been experimentally found to be largely non-random across brain areas. This means that certain connectivity motifs occur at a higher frequency than would be expected by chance. Of particular interest, short-term synaptic plasticity properties were found to colocalize with specific motifs: an over-expression of bidirectional motifs has been found in neuronal pairs where short-term facilitation dominates synaptic transmission among the neurons, whereas an over-expression of unidirectional motifs has been observed in neuronal pairs where short-term depression dominates. In previous work we found that, given a network with fixed short-term properties, the interaction between short- and long-term plasticity of synaptic transmission is sufficient for the emergence of specific motifs. Here, we introduce an error-driven learning mechanism for short-term plasticity that may explain how such observed correspondences develop from randomly initialized dynamic synapses. By allowing synapses to change their properties, neurons are able to adapt their own activity depending on an error signal. This results in more rich dynamics and also, provided that the learning mechanism is target-specific, leads to specialized groups of synapses projecting onto functionally different targets, qualitatively replicating the experimental results of Wang and collaborators.
@article{Mahmud2014,
author = {Mahmud, Mufti and Pulizzi, Rocco and Vasilaki, Eleni and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3389/fninf.2014.00026},
journal = {Front Neuroinform},
journal-full = {Frontiers in neuroinformatics},
keywords = {MEAs; batch analysis; cellular electrophysiology; embarrassingly parallel signal-processing; extracellular; substrate arrays of microelectrodes},
pages = {26},
pmc = {PMC3958706},
pmid = {24678297},
pst = {epublish},
title = {QSpike tools: a generic framework for parallel batch preprocessing of extracellular neuronal signals recorded by substrate microelectrode arrays},
volume = {8},
year = {2014},
bdsk-url-1 = {https://doi.org/10.3389/fninf.2014.00026}
}
Micro-Electrode Arrays (MEAs) have emerged as a mature technique to investigate brain (dys)functions in vivo and in in vitro animal models. Often referred to as "smart" Petri dishes, MEAs have demonstrated a great potential particularly for medium-throughput studies in vitro, both in academic and pharmaceutical industrial contexts. Enabling rapid comparison of ionic/pharmacological/genetic manipulations with control conditions, MEAs are employed to screen compounds by monitoring non-invasively the spontaneous and evoked neuronal electrical activity in longitudinal studies, with relatively inexpensive equipment. However, in order to acquire sufficient statistical significance, recordings last up to tens of minutes and generate large amount of raw data (e.g., 60 channels/MEA, 16 bits A/D conversion, 20 kHz sampling rate: approximately 8 GB/MEA,h uncompressed). Thus, when the experimental conditions to be tested are numerous, the availability of fast, standardized, and automated signal preprocessing becomes pivotal for any subsequent analysis and data archiving. To this aim, we developed an in-house cloud-computing system, named QSpike Tools, where CPU-intensive operations, required for preprocessing of each recorded channel (e.g., filtering, multi-unit activity detection, spike-sorting, etc.), are decomposed and batch-queued to a multi-core architecture or to a computers cluster. With the commercial availability of new and inexpensive high-density MEAs, we believe that disseminating QSpike Tools might facilitate its wide adoption and customization, and inspire the creation of community-supported cloud-computing facilities for MEAs users.
@article{Vasilaki2014,
author = {Vasilaki, Eleni and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1371/journal.pone.0084626},
journal = {PLoS One},
journal-full = {PloS one},
mesh = {Humans; Nerve Net; Neuronal Plasticity; Neurons; Synapses},
number = {1},
pages = {e84626},
pmc = {PMC3893143},
pmid = {24454735},
pst = {epublish},
title = {Emergence of connectivity motifs in networks of model neurons with short- and long-term plastic synapses},
volume = {9},
year = {2014},
bdsk-url-1 = {https://doi.org/10.1371/journal.pone.0084626}
}
Recent experimental data from the rodent cerebral cortex and olfactory bulb indicate that specific connectivity motifs are correlated with short-term dynamics of excitatory synaptic transmission. It was observed that neurons with short-term facilitating synapses form predominantly reciprocal pairwise connections, while neurons with short-term depressing synapses form predominantly unidirectional pairwise connections. The cause of these structural differences in excitatory synaptic microcircuits is unknown. We show that these connectivity motifs emerge in networks of model neurons, from the interactions between short-term synaptic dynamics (SD) and long-term spike-timing dependent plasticity (STDP). While the impact of STDP on SD was shown in simultaneous neuronal pair recordings in vitro, the mutual interactions between STDP and SD in large networks are still the subject of intense research. Our approach combines an SD phenomenological model with an STDP model that faithfully captures long-term plasticity dependence on both spike times and frequency. As a proof of concept, we first simulate and analyze recurrent networks of spiking neurons with random initial connection efficacies and where synapses are either all short-term facilitating or all depressing. For identical external inputs to the network, and as a direct consequence of internally generated activity, we find that networks with depressing synapses evolve unidirectional connectivity motifs, while networks with facilitating synapses evolve reciprocal connectivity motifs. We then show that the same results hold for heterogeneous networks, including both facilitating and depressing synapses. This does not contradict a recent theory that proposes that motifs are shaped by external inputs, but rather complements it by examining the role of both the external inputs and the internally generated network activity. Our study highlights the conditions under which SD-STDP might explain the correlation between facilitation and reciprocal connectivity motifs, as well as between depression and unidirectional motifs.
@article{Sekar2013,
author = {Sekar, S and Jonckers, E and Verhoye, M and Willems, R and Veraart, J and Van Audekerke, J and Couto, J and Giugliano, M and Wuyts, K and Dedeurwaerdere, S and Sijbers, J and Mackie, C and Ver Donck, L and Steckler, T and Van der Linden, A},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1007/s00213-013-2966-3},
journal = {Psychopharmacology (Berl)},
journal-full = {Psychopharmacology},
mesh = {Animals; Brain; Brain Mapping; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Magnetic Resonance Imaging; Male; Memantine; Motor Activity; Multimodal Imaging; Rats; Rats, Inbred Strains; Receptors, N-Methyl-D-Aspartate},
month = jun,
number = {3},
pages = {479-91},
pmid = {23354531},
pst = {ppublish},
title = {Subchronic memantine induced concurrent functional disconnectivity and altered ultra-structural tissue integrity in the rodent brain: revealed by multimodal MRI},
volume = {227},
year = {2013},
bdsk-url-1 = {https://doi.org/10.1007/s00213-013-2966-3}
}
BACKGROUND: An effective NMDA antagonist imaging model may find key utility in advancing schizophrenia drug discovery research. We investigated effects of subchronic treatment with the NMDA antagonist memantine by using behavioural observation and multimodal MRI. METHODS: Pharmacological MRI (phMRI) was used to map the neuroanatomical binding sites of memantine after acute and subchronic treatment. Resting state fMRI (rs-fMRI) and diffusion MRI were used to study the changes in functional connectivity (FC) and ultra-structural tissue integrity before and after subchronic memantine treatment. Further corroborating behavioural evidences were documented. RESULTS: Dose-dependent phMRI activation was observed in the prelimbic cortex following acute doses of memantine. Subchronic treatment revealed significant effects in the hippocampus, cingulate, prelimbic and retrosplenial cortices. Decreases in FC amongst the hippocampal and frontal cortical structures (prelimbic, cingulate) were apparent through rs-fMRI investigation, indicating a loss of connectivity. Diffusion kurtosis MRI showed decreases in fractional anisotropy and mean diffusivity changes, suggesting ultra-structural changes in the hippocampus and cingulate cortex. Limited behavioural assessment suggested that memantine induced behavioural effects comparable to other NMDA antagonists as measured by locomotor hyperactivity and that the effects could be reversed by antipsychotic drugs. CONCLUSION: Our findings substantiate the hypothesis that repeated NMDA receptor blockade with nonspecific, noncompetitive NMDA antagonists may lead to functional and ultra-structural alterations, particularly in the hippocampus and cingulate cortex. These changes may underlie the behavioural effects. Furthermore, the present findings underscore the utility and the translational potential of multimodal MR imaging and acute/subchronic memantine model in the search for novel disease-modifying treatments for schizophrenia.
@article{Espuny-Camacho2013,
author = {Espuny-Camacho, Ira and Michelsen, Kimmo A and Gall, David and Linaro, Daniele and Hasche, Anja and Bonnefont, J{\'e}r{\^o}me and Bali, Camilia and Orduz, David and Bilheu, Ang{\'e}line and Herpoel, Ad{\`e}le and Lambert, Nelle and Gaspard, Nicolas and P{\'e}ron, Sophie and Schiffmann, Serge N and Giugliano, Michele and Gaillard, Afsaneh and Vanderhaeghen, Pierre},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1016/j.neuron.2012.12.011},
journal = {Neuron},
journal-full = {Neuron},
mesh = {6-Cyano-7-nitroquinoxaline-2,3-dione; Age Factors; Animals; Axons; Brain; Bromodeoxyuridine; Calcium; Cell Differentiation; Cell Transplantation; Cells, Cultured; Dendrites; Embryonic Stem Cells; Evoked Potentials; Excitatory Amino Acid Antagonists; Female; Fetus; Fluorescent Dyes; Gene Expression Profiling; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Humans; In Vitro Techniques; Mice; Microscopy, Electron, Transmission; Microtubule-Associated Proteins; Nerve Net; Nerve Tissue Proteins; Oligonucleotide Array Sequence Analysis; Patch-Clamp Techniques; Pluripotent Stem Cells; Pregnancy; Pyramidal Cells; RNA, Messenger; Synapses; Synaptic Potentials; Transcription Factors; Transduction, Genetic; Tyrosine 3-Monooxygenase; Valine; Vesicular Glutamate Transport Protein 1},
month = feb,
number = {3},
pages = {440-56},
pmid = {23395372},
pst = {ppublish},
title = {Pyramidal neurons derived from human pluripotent stem cells integrate efficiently into mouse brain circuits in vivo},
volume = {77},
year = {2013},
bdsk-url-1 = {https://doi.org/10.1016/j.neuron.2012.12.011}
}
The study of human cortical development has major implications for brain evolution and diseases but has remained elusive due to paucity of experimental models. Here we found that human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), cultured without added morphogens, recapitulate corticogenesis leading to the sequential generation of functional pyramidal neurons of all six layer identities. After transplantation into mouse neonatal brain, human ESC-derived cortical neurons integrated robustly and established specific axonal projections and dendritic patterns corresponding to native cortical neurons. The differentiation and connectivity of the transplanted human cortical neurons complexified progressively over several months in vivo, culminating in the establishment of functional synapses with the host circuitry. Our data demonstrate that human cortical neurons generated in vitro from ESC/iPSC can develop complex hodological properties characteristic of the cerebral cortex in vivo, thereby offering unprecedented opportunities for the modeling of human cortex diseases and brain repair.
@article{Testa-Silva2012,
author = {Testa-Silva, Guilherme and Loebel, Alex and Giugliano, Michele and de Kock, Christiaan P J and Mansvelder, Huibert D and Meredith, Rhiannon M},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1093/cercor/bhr224},
journal = {Cereb Cortex},
journal-full = {Cerebral cortex (New York, N.Y. : 1991)},
mesh = {Animals; Autistic Disorder; Disease Models, Animal; Female; Intellectual Disability; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Net; Prefrontal Cortex; Synapses; Synaptic Transmission},
month = jun,
number = {6},
pages = {1333-42},
pmc = {PMC3561643},
pmid = {21856714},
pst = {ppublish},
title = {Hyperconnectivity and slow synapses during early development of medial prefrontal cortex in a mouse model for mental retardation and autism},
volume = {22},
year = {2012},
bdsk-url-1 = {https://doi.org/10.1093/cercor/bhr224}
}
Neuronal theories of neurodevelopmental disorders (NDDs) of autism and mental retardation propose that abnormal connectivity underlies deficits in attentional processing. We tested this theory by studying unitary synaptic connections between layer 5 pyramidal neurons within medial prefrontal cortex (mPFC) networks in the Fmr1-KO mouse model for mental retardation and autism. In line with predictions from neurocognitive theory, we found that neighboring pyramidal neurons were hyperconnected during a critical period in early mPFC development. Surprisingly, excitatory synaptic connections between Fmr1-KO pyramidal neurons were significantly slower and failed to recover from short-term depression as quickly as wild type (WT) synapses. By 4-5 weeks of mPFC development, connectivity rates were identical for both KO and WT pyramidal neurons and synapse dynamics changed from depressing to facilitating responses with similar properties in both groups. We propose that the early alteration in connectivity and synaptic recovery are tightly linked: using a network model, we show that slower synapses are essential to counterbalance hyperconnectivity in order to maintain a dynamic range of excitatory activity. However, the slow synaptic time constants induce decreased responsiveness to low-frequency stimulation, which may explain deficits in integration and early information processing in attentional neuronal networks in NDDs.
@article{Moroni2011,
author = {Moroni, Mirko and Biro, Istvan and Giugliano, Michele and Vijayan, Ranjit and Biggin, Philip C and Beato, Marco and Sivilotti, Lucia G},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1523/JNEUROSCI.1985-11.2011},
journal = {J Neurosci},
journal-full = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
mesh = {Animals; Chlorides; Extracellular Fluid; GABA Agonists; HEK293 Cells; Humans; Intracellular Fluid; Membrane Potentials; Models, Neurological; Patch-Clamp Techniques; Protein Structure, Tertiary; Rats; Receptors, GABA; Receptors, Glycine; Time Factors},
month = oct,
number = {40},
pages = {14095-106},
pmc = {PMC3204932},
pmid = {21976494},
pst = {ppublish},
title = {Chloride ions in the pore of glycine and GABA channels shape the time course and voltage dependence of agonist currents},
volume = {31},
year = {2011},
bdsk-url-1 = {https://doi.org/10.1523/JNEUROSCI.1985-11.2011}
}
In the vertebrate CNS, fast synaptic inhibition is mediated by GABA and glycine receptors. We recently reported that the time course of these synaptic currents is slower when intracellular chloride is high. Here we extend these findings to measure the effects of both extracellular and intracellular chloride on the deactivation of glycine and GABA currents at both negative and positive holding potentials. Currents were elicited by fast agonist application to outside-out patches from HEK-293 cells expressing rat glycine or GABA receptors. The slowing effect of high extracellular chloride on current decay was detectable only in low intracellular chloride (4 mm). Our main finding is that glycine and GABA receptors "sense" chloride concentrations because of interactions between the M2 pore-lining domain and the permeating ions. This hypothesis is supported by the observation that the sensitivity of channel gating to intracellular chloride is abolished if the channel is engineered to become cation selective or if positive charges in the external pore vestibule are eliminated by mutagenesis. The appropriate interaction between permeating ions and channel pore is also necessary to maintain the channel voltage sensitivity of gating, which prolongs current decay at depolarized potentials. Voltage dependence is abolished by the same mutations that suppress the effect of intracellular chloride and also by replacing chloride with another permeant ion, thiocyanate. These observations suggest that permeant chloride affects gating by a foot-in-the-door effect, binding to a channel site with asymmetrical access from the intracellular and extracellular sides of the membrane.
@article{Richmond2011,
author = {Richmond, Paul and Buesing, Lars and Giugliano, Michele and Vasilaki, Eleni},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1371/journal.pone.0018539},
journal = {PLoS One},
journal-full = {PloS one},
mesh = {Algorithms; Computer Graphics},
month = may,
number = {5},
pages = {e18539},
pmc = {PMC3087717},
pmid = {21572529},
pst = {epublish},
title = {Democratic population decisions result in robust policy-gradient learning: a parametric study with GPU simulations},
volume = {6},
year = {2011},
bdsk-url-1 = {https://doi.org/10.1371/journal.pone.0018539}
}
High performance computing on the Graphics Processing Unit (GPU) is an emerging field driven by the promise of high computational power at a low cost. However, GPU programming is a non-trivial task and moreover architectural limitations raise the question of whether investing effort in this direction may be worthwhile. In this work, we use GPU programming to simulate a two-layer network of Integrate-and-Fire neurons with varying degrees of recurrent connectivity and investigate its ability to learn a simplified navigation task using a policy-gradient learning rule stemming from Reinforcement Learning. The purpose of this paper is twofold. First, we want to support the use of GPUs in the field of Computational Neuroscience. Second, using GPU computing power, we investigate the conditions under which the said architecture and learning rule demonstrate best performance. Our work indicates that networks featuring strong Mexican-Hat-shaped recurrent connections in the top layer, where decision making is governed by the formation of a stable activity bump in the neural population (a "non-democratic" mechanism), achieve mediocre learning results at best. In absence of recurrent connections, where all neurons "vote" independently ("democratic") for a decision via population vector readout, the task is generally learned better and more robustly. Our study would have been extremely difficult on a desktop computer without the use of GPU programming. We present the routines developed for this purpose and show that a speed improvement of 5x up to 42x is provided versus optimised Python code. The higher speed is achieved when we exploit the parallelism of the GPU in the search of learning parameters. This suggests that efficient GPU programming can significantly reduce the time needed for simulating networks of spiking neurons, particularly when multiple parameter configurations are investigated.
@article{Linaro2011,
author = {Linaro, Daniele and Storace, Marco and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1371/journal.pcbi.1001102},
journal = {PLoS Comput Biol},
journal-full = {PLoS computational biology},
mesh = {Computer Simulation; Ion Channel Gating; Ion Channels; Markov Chains; Membrane Potentials; Models, Neurological; Neurons},
month = mar,
number = {3},
pages = {e1001102},
pmc = {PMC3053314},
pmid = {21423712},
pst = {ppublish},
title = {Accurate and fast simulation of channel noise in conductance-based model neurons by diffusion approximation},
volume = {7},
year = {2011},
bdsk-url-1 = {https://doi.org/10.1371/journal.pcbi.1001102}
}
Stochastic channel gating is the major source of intrinsic neuronal noise whose functional consequences at the microcircuit- and network-levels have been only partly explored. A systematic study of this channel noise in large ensembles of biophysically detailed model neurons calls for the availability of fast numerical methods. In fact, exact techniques employ the microscopic simulation of the random opening and closing of individual ion channels, usually based on Markov models, whose computational loads are prohibitive for next generation massive computer models of the brain. In this work, we operatively define a procedure for translating any Markov model describing voltage- or ligand-gated membrane ion-conductances into an effective stochastic version, whose computer simulation is efficient, without compromising accuracy. Our approximation is based on an improved Langevin-like approach, which employs stochastic differential equations and no Montecarlo methods. As opposed to an earlier proposal recently debated in the literature, our approximation reproduces accurately the statistical properties of the exact microscopic simulations, under a variety of conditions, from spontaneous to evoked response features. In addition, our method is not restricted to the Hodgkin-Huxley sodium and potassium currents and is general for a variety of voltage- and ligand-gated ion currents. As a by-product, the analysis of the properties emerging in exact Markov schemes by standard probability calculus enables us for the first time to analytically identify the sources of inaccuracy of the previous proposal, while providing solid ground for its modification and improvement we present here.
@article{Kunze2011,
author = {Kunze, Anja and Giugliano, Michele and Valero, Ana and Renaud, Philippe},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1016/j.biomaterials.2010.11.047},
journal = {Biomaterials},
journal-full = {Biomaterials},
mesh = {Alginates; Animals; Cell Culture Techniques; Cells, Cultured; Cerebral Cortex; Female; Glucuronic Acid; Hexuronic Acids; Hydrogels; Materials Testing; Microfluidics; Neurites; Neurons; Rats; Rats, Wistar; Sepharose; Tissue Scaffolds},
month = mar,
number = {8},
pages = {2088-98},
pmid = {21159379},
pst = {ppublish},
title = {Micropatterning neural cell cultures in 3D with a multi-layered scaffold},
volume = {32},
year = {2011},
bdsk-url-1 = {https://doi.org/10.1016/j.biomaterials.2010.11.047}
}
Cortical neurons, in their native state, are organized in six different cell layers; and the thickness of the cell layer ranges from 0.12 mm to 0.4 mm. The structure of cell layers plays an important role in neurodegenerative diseases or corticogenesis. We developed a 3D microfluidic device for creating physiologically realistic, micrometer scaled neural cell layers. Using this device, we demonstrated that (1) agarose-alginate mixture can be gelled thermally, thus an excellent candidate for forming multi-layered scaffolds for micropatterning embedded cells; (2) primary cortical neurons were cultured successfully for up to three weeks in the micropatterned multi-layered scaffold; (3) B27 concentration gradient enhanced neurite outgrowth. In addition, this device is compatible with optical microscopy, the dynamic process of neural growth can be imaged, and density and number of neurites can be quantified. This device can potentially be used for drug development, as well as research in basic neural biology.
@article{Fuchsberger2011,
author = {Fuchsberger, Kai and Le Goff, Alan and Gambazzi, Luca and Toma, Francesca Maria and Goldoni, Andrea and Giugliano, Michele and Stelzle, Martin and Prato, Maurizio},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1002/smll.201001640},
journal = {Small},
journal-full = {Small (Weinheim an der Bergstrasse, Germany)},
mesh = {Biosensing Techniques; Dielectric Spectroscopy; Microelectrodes; Nanotechnology; Nanotubes, Carbon},
month = feb,
number = {4},
pages = {524-30},
pmid = {21246714},
pst = {ppublish},
title = {Multiwalled carbon-nanotube-functionalized microelectrode arrays fabricated by microcontact printing: platform for studying chemical and electrical neuronal signaling},
volume = {7},
year = {2011},
bdsk-url-1 = {https://doi.org/10.1002/smll.201001640}
}
A facile method is proposed for the deposition of multiwalled carbon nanotube (MWCNT) layers onto microelectrode arrays by means of a microcontact printing technique, leading to the fabrication of MEAs characterized by well defined electrical and morphological properties. Using polydimethyl siloxane stamps, produced from different mold designs, a flexibility of printing is achieved that provides access to microscale, nanostructured electrodes. The thickness of MWCNT layers can be exactly predetermined by evaluating the concentration of the MWCNT solution employed in the process. The electrode morphology is further characterized using laser scanning and scanning electron microscopy. Next, by means of impedance spectroscopy analysis, the MWCNT-electrode contact resistance and MWCNT film resistance is measured, while electrochemical impedance spectroscopy is used to estimate the obtained electrode-electrolyte interface. Structural and electrochemical properties make these electrodes suitable for electrical stimulation and recording of neurons and electrochemical detection of dopamine. MWCNT-functionalized electrodes show the ability to detect micromolar amounts of dopamine with a sensitivity of 19 nA μm(-1) . In combination with their biosensing properties, preliminary electrophysiological measurements show that MWCNT microelectrodes have recording properties superior to those of commercial TiN microelectrodes when detecting neuronal electrical activity under long-term cell-culture conditions. MWCNT-functionalized microelectrode arrays fabricated by microcontact printing represent a versatile and multipurpose platform for cell-culture monitoring.
@article{Robberechts2010,
author = {Robberechts, Quinten and Wijnants, Mike and Giugliano, Michele and De Schutter, Erik},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1152/jn.00030.2010},
journal = {J Neurophysiol},
journal-full = {Journal of neurophysiology},
mesh = {Animals; Cerebellar Cortex; Cyclic AMP-Dependent Protein Kinases; Electric Stimulation; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Glutamic Acid; Interneurons; Long-Term Synaptic Depression; Nerve Fibers; Patch-Clamp Techniques; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate; Receptors, N-Methyl-D-Aspartate; Synapses},
month = dec,
number = {6},
pages = {3413-23},
pmc = {PMC3007626},
pmid = {20861429},
pst = {ppublish},
title = {Long-term depression at parallel fiber to Golgi cell synapses},
volume = {104},
year = {2010},
bdsk-url-1 = {https://doi.org/10.1152/jn.00030.2010}
}
Golgi cells (GoCs) are the primary inhibitory interneurons of the granular layer of the cerebellum. Their inhibition of granule cells is central to operate the relay of excitatory inputs to the cerebellar cortex. Parallel fibers (PFs) establish synapses to the GoCs in the molecular layer; these synapses contain AMPA, N-methyl-D-aspartate (NMDA), and mostly group II metabotropic glutamate receptors. Long-term changes in the efficacy of synaptic transmission at the PF-GoC synapse have not been described previously. We used whole cell patch-clamp recordings of GoCs in acute rat cerebellar slices to study synaptic plasticity. We report that high-frequency burst stimulation of PFs, using a current-clamp or voltage-clamp induction protocol, gave rise to long-term depression (LTD) at the PF-GoC synapse. This form of LTD was not associated with persistent changes of paired-pulse ratio, suggesting a postsynaptic origin. Furthermore, LTD induction was not dependent on activation of NMDA receptors. PF-GoC LTD does require activation of specifically group II metabotropic glutamate receptors and of protein kinase A.
@article{Gambazzi2010,
author = {Gambazzi, Luca and Gokce, Ozgun and Seredenina, Tamara and Katsyuba, Elena and Runne, Heike and Markram, Henry and Giugliano, Michele and Luthi-Carter, Ruth},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1124/jpet.110.167551},
journal = {J Pharmacol Exp Ther},
journal-full = {The Journal of pharmacology and experimental therapeutics},
mesh = {Animals; Brain-Derived Neurotrophic Factor; Cerebral Cortex; Genetic Vectors; Huntingtin Protein; Huntington Disease; Immunohistochemistry; Lentivirus; Microelectrodes; Models, Statistical; Mutation; Nerve Net; Nerve Tissue Proteins; Neural Pathways; Neurons; Nuclear Proteins; Peptide Fragments; RNA; Rats; Rats, Wistar; Receptor, trkB; Reverse Transcriptase Polymerase Chain Reaction; Synapses},
month = oct,
number = {1},
pages = {13-22},
pmid = {20624994},
pst = {ppublish},
title = {Diminished activity-dependent brain-derived neurotrophic factor expression underlies cortical neuron microcircuit hypoconnectivity resulting from exposure to mutant huntingtin fragments},
volume = {335},
year = {2010},
bdsk-url-1 = {https://doi.org/10.1124/jpet.110.167551}
}
Although previous studies of Huntington’s disease (HD) have addressed many potential mechanisms of striatal neuron dysfunction and death, it is also known, based on clinical findings, that cortical function is dramatically disrupted in HD. With respect to disease etiology, however, the specific molecular and neuronal circuit bases for the cortical effects of mutant huntingtin (htt) have remained largely unknown. In the present work, we studied the relationship between the molecular effects of mutant htt fragments in cortical cells and the corresponding behavior of cortical neuron microcircuits by using a novel cellular model of HD. We observed that a transcript-selective diminution in activity-dependent brain-derived neurotrophic factor (BDNF) expression preceded the onset of a synaptic connectivity deficit in ex vivo cortical networks, which manifested as decreased spontaneous collective burst-firing behavior measured by multielectrode array substrates. Decreased BDNF expression was determined to be a significant contributor to network-level dysfunction, as shown by the ability of exogenous BDNF to ameliorate cortical microcircuit burst firing. The molecular determinants of the dysregulation of activity-dependent BDNF expression by mutant htt seem to be distinct from previously elucidated mechanisms, because they do not involve known neuron-restrictive silencer factor/RE1-silencing transcription factor-regulated promoter sequences but instead result from dysregulation of BDNF exon IV and VI transcription. These data elucidate a novel HD-related deficit in BDNF gene regulation as a plausible mechanism of cortical neuron hypoconnectivity and cortical function deficits in HD. Moreover, the novel model paradigm established here is well suited to further mechanistic and drug screening research applications.
@article{Talpalar2010,
author = {Talpalar, Adolfo E and Giugliano, Michele and Grossman, Yoram},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3389/fncel.2010.00128},
journal = {Front Cell Neurosci},
journal-full = {Frontiers in cellular neuroscience},
keywords = {HPNS; dentate gyrus; entorhinal cortex; granule cells; hippocampus; hyperbaric helium pressure; rat; synaptic dynamics},
pages = {128},
pmc = {PMC2967425},
pmid = {21048901},
pst = {epublish},
title = {Enduring medial perforant path short-term synaptic depression at high pressure},
volume = {4},
year = {2010},
bdsk-url-1 = {https://doi.org/10.3389/fncel.2010.00128}
}
The high pressure neurological syndrome develops during deep-diving (>1.1 MPa) involving impairment of cognitive functions, alteration of synaptic transmission and increased excitability in cortico-hippocampal areas. The medial perforant path (MPP), connecting entorhinal cortex with the hippocampal formation, displays synaptic frequency-dependent-depression (FDD) under normal conditions. Synaptic FDD is essential for specific functions of various neuronal networks. We used rat cortico-hippocampal slices and computer simulations for studying the effects of pressure and its interaction with extracellular Ca(2+) ([Ca(2+)](o)) on FDD at the MPP synapses. At atmospheric pressure, high [Ca(2+)](o) (4-6 mM) saturated single MPP field EPSP (fEPSP) and increased FDD in response to short trains at 50 Hz. High pressure (HP; 10.1 MPa) depressed single fEPSPs by 50%. Increasing [Ca(2+)](o) to 4 mM at HP saturated synaptic response at a subnormal level (only 20% recovery of single fEPSPs), but generated a FDD similar to atmospheric pressure. Mathematical model analysis of the fractions of synaptic resources used by each fEPSP during trains (normalized to their maximum) and the total fraction utilized within a train indicate that HP depresses synaptic activity also by reducing synaptic resources. This data suggest that MPP synapses may be modulated, in addition to depression of single events, by reduction of synaptic resources and then may have the ability to conserve their dynamic properties under different conditions.
@article{Sucapane2009,
author = {Sucapane, Antonietta and Cellot, Giada and Prato, Maurizio and Giugliano, Michele and Parpura, Vladimir and Ballerini, Laura},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1166/jns.2009.002},
journal = {J Nanoneurosci},
journal-full = {Journal of nanoneuroscience},
month = jun,
number = {1},
pages = {10-16},
pmc = {PMC2768360},
pmid = {19865604},
pst = {ppublish},
title = {Interactions Between Cultured Neurons and Carbon Nanotubes: A Nanoneuroscience Vignette},
volume = {1},
year = {2009},
bdsk-url-1 = {https://doi.org/10.1166/jns.2009.002}
}
Carbon nanotubes, owing to their electrical, chemical, mechanical, and thermal properties, are one of the most promising nanomaterials for the electronics, computer, and aerospace industries. More recently, these unique materials are finding their niche in neuroscience. Here, we discuss the use of carbon nanotubes as scaffolds for neuronal growth. The chemical properties of carbon nanotubes can be systematically varied by attaching different functional groups. Such functionalized carbon nanotubes can be used to control the outgrowth and branching pattern of neuronal processes. We also discuss electrical interactions between neurons and carbon nanotubes. The electrical properties of nanotubes can provide a mechanism to monitor or stimulate neurons through the scaffold itself. The ease of which carbon nanotubes can be patterned makes them attractive for studying the organization of neural networks and has the potential to develop new devices for neural prosthesis. We note that additional toxicity studies of carbon nanotubes are necessary so that exposure guidelines and safety regulations can be set.
@article{Cellot2009,
author = {Cellot, Giada and Cilia, Emanuele and Cipollone, Sara and Rancic, Vladimir and Sucapane, Antonella and Giordani, Silvia and Gambazzi, Luca and Markram, Henry and Grandolfo, Micaela and Scaini, Denis and Gelain, Fabrizio and Casalis, Loredana and Prato, Maurizio and Giugliano, Michele and Ballerini, Laura},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1038/nnano.2008.374},
journal = {Nat Nanotechnol},
journal-full = {Nature nanotechnology},
mesh = {Action Potentials; Animals; Biocompatible Materials; Cell Adhesion; Cells, Cultured; Electric Capacitance; Electric Stimulation; Microscopy, Electron, Scanning; Nanotechnology; Nanotubes, Carbon; Neural Conduction; Neurons; Patch-Clamp Techniques; Rats; Tissue Scaffolds},
month = feb,
number = {2},
pages = {126-33},
pmid = {19197316},
pst = {ppublish},
title = {Carbon nanotubes might improve neuronal performance by favouring electrical shortcuts},
volume = {4},
year = {2009},
bdsk-url-1 = {https://doi.org/10.1038/nnano.2008.374}
}
Carbon nanotubes have been applied in several areas of nerve tissue engineering to probe and augment cell behaviour, to label and track subcellular components, and to study the growth and organization of neural networks. Recent reports show that nanotubes can sustain and promote neuronal electrical activity in networks of cultured cells, but the ways in which they affect cellular function are still poorly understood. Here, we show, using single-cell electrophysiology techniques, electron microscopy analysis and theoretical modelling, that nanotubes improve the responsiveness of neurons by forming tight contacts with the cell membranes that might favour electrical shortcuts between the proximal and distal compartments of the neuron. We propose the ’electrotonic hypothesis’ to explain the physical interactions between the cell and nanotube, and the mechanisms of how carbon nanotubes might affect the collective electrical activity of cultured neuronal networks. These considerations offer a perspective that would allow us to predict or engineer interactions between neurons and carbon nanotubes.
@article{Gawad2009,
author = {Gawad, Shady and Giugliano, Michele and Heuschkel, Marc and Wessling, B{\"o}rge and Markram, Henry and Schnakenberg, Uwe and Renaud, Philippe and Morgan, Hywel},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3389/neuro.16.001.2009},
journal = {Front Neuroeng},
journal-full = {Frontiers in neuroengineering},
keywords = {cortex; electrophysiology; extracellular recordings; impedance spectroscopy; neurons; substrate microelectrodes},
pages = {1},
pmc = {PMC2634525},
pmid = {19194527},
pst = {epublish},
title = {Substrate arrays of iridium oxide microelectrodes for in vitro neuronal interfacing},
volume = {2},
year = {2009},
bdsk-url-1 = {https://doi.org/10.3389/neuro.16.001.2009}
}
The design of novel bidirectional interfaces for in vivo and in vitro nervous systems is an important step towards future functional neuroprosthetics. Small electrodes, structures and devices are necessary to achieve high-resolution and target-selectivity during stimulation and recording of neuronal networks, while significant charge transfer and large signal-to-noise ratio are required for accurate time resolution. In addition, the physical properties of the interface should remain stable across time, especially when chronic in vivo applications or in vitro long-term studies are considered, unless a procedure to actively compensate for degradation is provided. In this short report, we describe the use and fabrication of arrays of 120 planar microelectrodes (MEAs) of sputtered Iridium Oxide (IrOx). The effective surface area of individual microelectrodes is significantly increased using electrochemical activation, a procedure that may also be employed to restore the properties of the electrodes as required. The electrode activation results in a very low interface impedance, especially in the lower frequency domain, which was characterized by impedance spectroscopy. The increase in the roughness of the microelectrodes surface was imaged using digital holographic microscopy and electron microscopy. Aging of the activated electrodes was also investigated, comparing storage in saline with storage in air. Demonstration of concept was achieved by recording multiple single-unit spike activity in acute brain slice preparations of rat neocortex. Data suggests that extracellular recording of action potentials can be achieved with planar IrOx MEAs with good signal-to-noise ratios.
@article{Giugliano2009,
author = {Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.3389/neuro.01.019.2009},
journal = {Front Neurosci},
journal-full = {Frontiers in neuroscience},
number = {2},
pages = {160-1},
pmc = {PMC2751621},
pmid = {20228859},
pst = {epublish},
title = {Calcium waves in astrocyte networks: theory and experiments},
volume = {3},
year = {2009},
bdsk-url-1 = {https://doi.org/10.3389/neuro.01.019.2009}
}
@article{Giugliano2008,
author = {Giugliano, Michele and La Camera, Giancarlo and Fusi, Stefano and Senn, Walter},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1007/s00422-008-0270-9},
journal = {Biol Cybern},
journal-full = {Biological cybernetics},
mesh = {Animals; Cerebral Cortex; Humans; Models, Neurological; Neural Networks, Computer; Neurons},
month = nov,
number = {4-5},
pages = {303-18},
pmid = {19011920},
pst = {ppublish},
title = {The response of cortical neurons to in vivo-like input current: theory and experiment: II. Time-varying and spatially distributed inputs},
volume = {99},
year = {2008},
bdsk-url-1 = {https://doi.org/10.1007/s00422-008-0270-9}
}
The response of a population of neurons to time-varying synaptic inputs can show a rich phenomenology, hardly predictable from the dynamical properties of the membrane’s inherent time constants. For example, a network of neurons in a state of spontaneous activity can respond significantly more rapidly than each single neuron taken individually. Under the assumption that the statistics of the synaptic input is the same for a population of similarly behaving neurons (mean field approximation), it is possible to greatly simplify the study of neural circuits, both in the case in which the statistics of the input are stationary (reviewed in La Camera et al. in Biol Cybern, 2008) and in the case in which they are time varying and unevenly distributed over the dendritic tree. Here, we review theoretical and experimental results on the single-neuron properties that are relevant for the dynamical collective behavior of a population of neurons. We focus on the response of integrate-and-fire neurons and real cortical neurons to long-lasting, noisy, in vivo-like stationary inputs and show how the theory can predict the observed rhythmic activity of cultures of neurons. We then show how cortical neurons adapt on multiple time scales in response to input with stationary statistics in vitro. Next, we review how it is possible to study the general response properties of a neural circuit to time-varying inputs by estimating the response of single neurons to noisy sinusoidal currents. Finally, we address the dendrite-soma interactions in cortical neurons leading to gain modulation and spike bursts, and show how these effects can be captured by a two-compartment integrate-and-fire neuron. Most of the experimental results reviewed in this article have been successfully reproduced by simple integrate-and-fire model neurons.
@article{La-Camera2008,
author = {La Camera, Giancarlo and Giugliano, Michele and Senn, Walter and Fusi, Stefano},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1007/s00422-008-0272-7},
journal = {Biol Cybern},
journal-full = {Biological cybernetics},
mesh = {Animals; Cerebral Cortex; Humans; Models, Neurological; Neurons},
month = nov,
number = {4-5},
pages = {279-301},
pmid = {18985378},
pst = {ppublish},
title = {The response of cortical neurons to in vivo-like input current: theory and experiment : I. Noisy inputs with stationary statistics},
volume = {99},
year = {2008},
bdsk-url-1 = {https://doi.org/10.1007/s00422-008-0272-7}
}
The study of several aspects of the collective dynamics of interacting neurons can be highly simplified if one assumes that the statistics of the synaptic input is the same for a large population of similarly behaving neurons (mean field approach). In particular, under such an assumption, it is possible to determine and study all the equilibrium points of the network dynamics when the neuronal response to noisy, in vivo-like, synaptic currents is known. The response function can be computed analytically for simple integrate-and-fire neuron models and it can be measured directly in experiments in vitro. Here we review theoretical and experimental results about the neural response to noisy inputs with stationary statistics. These response functions are important to characterize the collective neural dynamics that are proposed to be the neural substrate of working memory, decision making and other cognitive functions. Applications to the case of time-varying inputs are reviewed in a companion paper (Giugliano et al. in Biol Cybern, 2008). We conclude that modified integrate-and-fire neuron models are good enough to reproduce faithfully many of the relevant dynamical aspects of the neuronal response measured in experiments on real neurons in vitro.
@article{Kondgen2008,
author = {K{\"o}ndgen, Harold and Geisler, Caroline and Fusi, Stefano and Wang, Xiao-Jing and L{\"u}scher, Hans-Rudolf and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1093/cercor/bhm235},
journal = {Cereb Cortex},
journal-full = {Cerebral cortex (New York, N.Y. : 1991)},
mesh = {Action Potentials; Animals; Artifacts; Electric Stimulation; Evoked Potentials; Linear Models; Models, Neurological; Neocortex; Organ Culture Techniques; Periodicity; Pyramidal Cells; Rats; Rats, Wistar; Reaction Time; Somatosensory Cortex},
month = sep,
number = {9},
pages = {2086-97},
pmc = {PMC3140196},
pmid = {18263893},
pst = {ppublish},
title = {The dynamical response properties of neocortical neurons to temporally modulated noisy inputs in vitro},
volume = {18},
year = {2008},
bdsk-url-1 = {https://doi.org/10.1093/cercor/bhm235}
}
Cortical neurons are often classified by current-frequency relationship. Such a static description is inadequate to interpret neuronal responses to time-varying stimuli. Theoretical studies suggested that single-cell dynamical response properties are necessary to interpret ensemble responses to fast input transients. Further, it was shown that input-noise linearizes and boosts the response bandwidth, and that the interplay between the barrage of noisy synaptic currents and the spike-initiation mechanisms determine the dynamical properties of the firing rate. To test these model predictions, we estimated the linear response properties of layer 5 pyramidal cells by injecting a superposition of a small-amplitude sinusoidal wave and a background noise. We characterized the evoked firing probability across many stimulation trials and a range of oscillation frequencies (1-1000 Hz), quantifying response amplitude and phase-shift while changing noise statistics. We found that neurons track unexpectedly fast transients, as their response amplitude has no attenuation up to 200 Hz. This cut-off frequency is higher than the limits set by passive membrane properties (approximately 50 Hz) and average firing rate (approximately 20 Hz) and is not affected by the rate of change of the input. Finally, above 200 Hz, the response amplitude decays as a power-law with an exponent that is independent of voltage fluctuations induced by the background noise.
@article{Cali2008,
author = {Cal{\`\i}, Corrado and Berger, Thomas K and Pignatelli, Michele and Carleton, Alan and Markram, Henry and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1007/s10827-007-0058-2},
journal = {J Comput Neurosci},
journal-full = {Journal of computational neuroscience},
mesh = {Animals; Electric Conductivity; Electric Impedance; Electrophysiology; Gap Junctions; Models, Neurological; Nerve Net; Neurons; Rats; Rats, Wistar; Reaction Time; Sensory Thresholds; Somatosensory Cortex; Synapses},
month = jun,
number = {3},
pages = {330-45},
pmid = {18044016},
pst = {ppublish},
title = {Inferring connection proximity in networks of electrically coupled cells by subthreshold frequency response analysis},
volume = {24},
year = {2008},
bdsk-url-1 = {https://doi.org/10.1007/s10827-007-0058-2}
}
Electrical synapses continuously transfer signals bi-directionally from one cell to another, directly or indirectly via intermediate cells. Electrical synapses are common in many brain structures such as the inferior olive, the subcoeruleus nucleus and the neocortex, between neurons and between glial cells. In the cortex, interneurons have been shown to be electrically coupled and proposed to participate in large, continuous cortical syncytia, as opposed to smaller spatial domains of electrically coupled cells. However, to explore the significance of these findings it is imperative to map the electrical synaptic microcircuits, in analogy with in vitro studies on monosynaptic and disynaptic chemical coupling. Since "walking" from cell to cell over large distances with a glass pipette is challenging, microinjection of (fluorescent) dyes diffusing through gap-junctions remains so far the only method available to decipher such microcircuits even though technical limitations exist. Based on circuit theory, we derive analytical descriptions of the AC electrical coupling in networks of isopotential cells. We then suggest an operative electrophysiological protocol to distinguish between direct electrical connections and connections involving one or more intermediate cells. This method allows inferring the number of intermediate cells, generalizing the conventional coupling coefficient, which provides limited information. We validate our method through computer simulations, theoretical and numerical methods and electrophysiological paired recordings.
@article{Arsiero2007,
author = {Arsiero, M and L{\"u}scher, H-R and Giugliano, M},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
journal = {Arch Ital Biol},
journal-full = {Archives italiennes de biologie},
mesh = {Animals; Central Nervous System; Electrophysiology; History, 20th Century; Interdisciplinary Communication; Models, Neurological; Nerve Net; Neurons; Neurophysiology; Patch-Clamp Techniques; Signal Processing, Computer-Assisted},
month = nov,
number = {3-4},
pages = {193-209},
pmid = {18075116},
pst = {ppublish},
title = {Real-time closed-loop electrophysiology: towards new frontiers in in vitro investigations in the neurosciences},
volume = {145},
year = {2007}
}
Reflected at any level of organization of the central nervous system, most of the processes ranging from ion channels to neuronal networks occur in a closed loop, where the input to the system depends on its output. In contrast, most in vitro preparations and experimental protocols operate autonomously, and do not depend on the output of the studied system. Thanks to the progress in digital signal processing and real-time computing, it is now possible to artificially close the loop and investigate biophysical processes and mechanisms under increased realism. In this contribution, we review some of the most relevant examples of a new trend in in vitro electrophysiology, ranging from the use of dynamic-clamp to multi-electrode distributed feedback stimulation. We are convinced these represents the beginning of new frontiers for the in vitro investigation of the brain, promising to open the still existing borders between theoretical and experimental approaches while taking advantage of cutting edge technologies.
@article{Mazzatenta2007,
author = {Mazzatenta, Andrea and Giugliano, Michele and Campidelli, Stephane and Gambazzi, Luca and Businaro, Luca and Markram, Henry and Prato, Maurizio and Ballerini, Laura},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1523/JNEUROSCI.1051-07.2007},
journal = {J Neurosci},
journal-full = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
mesh = {Action Potentials; Animals; Animals, Newborn; Cell Culture Techniques; Electric Stimulation; Hippocampus; Microscopy, Electron, Scanning; Models, Neurological; Nanotechnology; Nanotubes, Carbon; Neural Pathways; Neurons; Organ Culture Techniques; Patch-Clamp Techniques; Prostheses and Implants; Rats; Rats, Sprague-Dawley; Synaptic Transmission},
month = jun,
number = {26},
pages = {6931-6},
pmc = {PMC6672220},
pmid = {17596441},
pst = {ppublish},
title = {Interfacing neurons with carbon nanotubes: electrical signal transfer and synaptic stimulation in cultured brain circuits},
volume = {27},
year = {2007},
bdsk-url-1 = {https://doi.org/10.1523/JNEUROSCI.1051-07.2007}
}
The unique properties of single-wall carbon nanotubes (SWNTs) and the application of nanotechnology to the nervous system may have a tremendous impact in the future developments of microsystems for neural prosthetics as well as immediate benefits for basic research. Despite increasing interest in neuroscience nanotechnologies, little is known about the electrical interactions between nanomaterials and neurons. We developed an integrated SWNT-neuron system to test whether electrical stimulation delivered via SWNT can induce neuronal signaling. To that aim, hippocampal cells were grown on pure SWNT substrates and patch clamped. We compared neuronal responses to voltage steps delivered either via conductive SWNT substrates or via the patch pipette. Our experimental results, supported by mathematical models to describe the electrical interactions occurring in SWNT-neuron hybrid systems, clearly indicate that SWNTs can directly stimulate brain circuit activity.
@article{Arsiero2007a,
author = {Arsiero, Maura and L{\"u}scher, Hans-Rudolf and Lundstrom, Brian Nils and Giugliano, Michele},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1523/JNEUROSCI.4937-06.2007},
journal = {J Neurosci},
journal-full = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
mesh = {Action Potentials; Animals; Electric Stimulation; Nerve Net; Neurons; Prefrontal Cortex; Rats; Rats, Wistar},
month = mar,
number = {12},
pages = {3274-84},
pmc = {PMC6672485},
pmid = {17376988},
pst = {ppublish},
title = {The impact of input fluctuations on the frequency-current relationships of layer 5 pyramidal neurons in the rat medial prefrontal cortex},
volume = {27},
year = {2007},
bdsk-url-1 = {https://doi.org/10.1523/JNEUROSCI.4937-06.2007}
}
The role of irregular cortical firing in neuronal computation is still debated, and it is unclear how signals carried by fluctuating synaptic potentials are decoded by downstream neurons. We examined in vitro frequency versus current (f-I) relationships of layer 5 (L5) pyramidal cells of the rat medial prefrontal cortex (mPFC) using fluctuating stimuli. Studies in the somatosensory cortex show that L5 neurons become insensitive to input fluctuations as input mean increases and that their f-I response becomes linear. In contrast, our results show that mPFC L5 pyramidal neurons retain an increased sensitivity to input fluctuations, whereas their sensitivity to the input mean diminishes to near zero. This implies that the discharge properties of L5 mPFC neurons are well suited to encode input fluctuations rather than input mean in their firing rates, with important consequences for information processing and stability of persistent activity at the network level.
@article{Berger2006,
author = {Berger, T and L{\"u}scher, H-R and Giugliano, M},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1016/j.neuroscience.2006.03.003},
journal = {Neuroscience},
journal-full = {Neuroscience},
mesh = {Animals; Animals, Newborn; Excitatory Postsynaptic Potentials; In Vitro Techniques; Nerve Net; Rats; Rats, Wistar; Somatosensory Cortex},
month = jul,
number = {4},
pages = {1401-13},
pmid = {16632207},
pst = {ppublish},
title = {Transient rhythmic network activity in the somatosensory cortex evoked by distributed input in vitro},
volume = {140},
year = {2006},
bdsk-url-1 = {https://doi.org/10.1016/j.neuroscience.2006.03.003}
}
The initiation and maintenance of physiological and pathophysiological oscillatory activity depends on the synaptic interactions within neuronal networks. We studied the mechanisms underlying evoked transient network oscillation in acute slices of the adolescent rat somatosensory cortex and modeled its underpinning mechanisms. Oscillations were evoked by brief spatially distributed noisy extracellular stimulation, delivered via bipolar electrodes. Evoked transient network oscillation was detected with multi-neuron patch-clamp recordings under different pharmacological conditions. The observed oscillations are in the frequency range of 2-5 Hz and consist of 4-12 mV large, 40-150 ms wide compound synaptic events with rare overlying action potentials. This evoked transient network oscillation is only weakly expressed in the somatosensory cortex and requires increased [K+]o of 6.25 mM and decreased [Ca2+]o of 1.5 mM and [Mg2+]o of 0.5 mM. A peak in the cross-correlation among membrane potential in layers II/III, IV and V neurons reflects the underlying network-driven basis of the evoked transient network oscillation. The initiation of the evoked transient network oscillation is accompanied by an increased [K+]o and can be prevented by the K+ channel blocker quinidine. In addition, a shift of the chloride reversal potential takes place during stimulation, resulting in a depolarizing type A GABA (GABAA) receptor response. Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionate (AMPA), N-methyl-D-aspartate (NMDA), or GABA(A) receptors as well as gap junctions prevents evoked transient network oscillation while a reduction of AMPA or GABA(A) receptor desensitization increases its duration and amplitude. The apparent reversal potential of -27 mV of the evoked transient network oscillation, its pharmacological profile, as well as the modeling results suggest a mixed contribution of glutamatergic, excitatory GABAergic, and gap junctional conductances in initiation and maintenance of this oscillatory activity. With these properties, evoked transient network oscillation resembles epileptic afterdischarges more than any other form of physiological or pathophysiological neocortical oscillatory activity.
@article{Giugliano2004,
author = {Giugliano, M and Darbon, P and Arsiero, M and L{\"u}scher, H-R and Streit, J},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1152/jn.00067.2004},
journal = {J Neurophysiol},
journal-full = {Journal of neurophysiology},
mesh = {Action Potentials; Animals; Animals, Newborn; Artifacts; Cells, Cultured; Cellular Senescence; Computer Simulation; Differential Threshold; Electrophysiology; Microelectrodes; Models, Neurological; Neocortex; Nerve Net; Neurons; Patch-Clamp Techniques; Rats; Rats, Wistar; Reaction Time},
month = aug,
number = {2},
pages = {977-96},
pmid = {15044515},
pst = {ppublish},
title = {Single-neuron discharge properties and network activity in dissociated cultures of neocortex},
volume = {92},
year = {2004},
bdsk-url-1 = {https://doi.org/10.1152/jn.00067.2004}
}
Cultures of neurons from rat neocortex exhibit spontaneous, temporally patterned, network activity. Such a distributed activity in vitro constitutes a possible framework for combining theoretical and experimental approaches, linking the single-neuron discharge properties to network phenomena. In this work, we addressed the issue of closing the loop, from the identification of the single-cell discharge properties to the prediction of collective network phenomena. Thus, we compared these predictions with the spontaneously emerging network activity in vitro, detected by substrate arrays of microelectrodes. Therefore, we characterized the single-cell discharge properties to Gauss-distributed noisy currents, under pharmacological blockade of the synaptic transmission. Such stochastic currents emulate a realistic input from the network. The mean (m) and variance (s(2)) of the injected current were varied independently, reminiscent of the extended mean-field description of a variety of possible presynaptic network organizations and mean activity levels, and the neuronal response was evaluated in terms of the steady-state mean firing rate (f). Experimental current-to-spike-rate responses f(m, s(2)) were similar to those of neurons in brain slices, and could be quantitatively described by leaky integrate-and-fire (IF) point neurons. The identified model parameters were then used in numerical simulations of a network of IF neurons. Such a network reproduced a collective activity, matching the spontaneous irregular population bursting, observed in cultured networks. We finally interpret such a collective activity and its link with model details by the mean-field theory. We conclude that the IF model is an adequate minimal description of synaptic integration and neuronal excitability, when collective network activities are considered in vitro.
@article{Reutimann2003,
author = {Reutimann, Jan and Giugliano, Michele and Fusi, Stefano},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1162/08997660360581912},
journal = {Neural Comput},
journal-full = {Neural computation},
mesh = {Action Potentials; Algorithms; Computer Simulation; Evoked Potentials; Models, Neurological; Motor Neurons; Neurons, Afferent; Stochastic Processes},
month = apr,
number = {4},
pages = {811-30},
pmid = {12689388},
pst = {ppublish},
title = {Event-driven simulation of spiking neurons with stochastic dynamics},
volume = {15},
year = {2003},
bdsk-url-1 = {https://doi.org/10.1162/08997660360581912}
}
We present a new technique, based on a proposed event-based strategy (Mattia & Del Giudice, 2000), for efficiently simulating large networks of simple model neurons. The strategy was based on the fact that interactions among neurons occur by means of events that are well localized in time (the action potentials) and relatively rare. In the interval between two of these events, the state variables associated with a model neuron or a synapse evolved deterministically and in a predictable way. Here, we extend the event-driven simulation strategy to the case in which the dynamics of the state variables in the inter-event intervals are stochastic. This extension captures both the situation in which the simulated neurons are inherently noisy and the case in which they are embedded in a very large network and receive a huge number of random synaptic inputs. We show how to effectively include the impact of large background populations into neuronal dynamics by means of the numerical evaluation of the statistical properties of single-model neurons under random current injection. The new simulation strategy allows the study of networks of interacting neurons with an arbitrary number of external afferents and inherent stochastic dynamics.
@article{Giugliano2000,
author = {Giugliano, M and Bove, M and Grattarola, M},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1109/10.841333},
journal = {IEEE Trans Biomed Eng},
journal-full = {IEEE transactions on bio-medical engineering},
mesh = {Computer Simulation; Electrophysiology; Glucose; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Markov Chains; Mathematics; Models, Biological},
month = may,
number = {5},
pages = {611-23},
pmid = {10851805},
pst = {ppublish},
title = {Insulin release at the molecular level: metabolic-electrophysiological modeling of the pancreatic beta-cells},
volume = {47},
year = {2000},
bdsk-url-1 = {https://doi.org/10.1109/10.841333}
}
The role of pancreatic beta-cells is fundamental in the control endocrine system, maintaining the blood glucose homeostais in a physiological regime, via the glucose-induced release of insulin. An increasing amount of detailed experimental evidences at the cellular and molecular biology levels have been collected on the key factors determining the insulin release by the pancreatic beta-cells. The direct transposition of such experimental data into accurate mathematical descriptions might contribute to considerably clarify the impact of each cellular component on the global glucose metabolism. Under these perspectives, we model and computer-simulate the stimulus-secretion coupling in beta-cells by describing four interacting cellular subsystems, consisting in the glucose transport and metabolism, the excitable electrophysiological behavior, the dynamics of the intracellular calcium ions, and the exocytosis of granules containing insulin. We explicit the molecular nature of each subsystem, expressing the mutual relationships and the feedbacks that determine the metabolic-electrophysiological behavior of an isolated beta-cell. Finally, we discuss the simulation results of the behavior of isolated beta-cells as well as of population of electrically coupled beta-cells in Langerhans islets, under physiological and pathological conditions, including noninsulin-dependent diabetes mellitus (NIDDM) and hyperinsulinemic hypoglycaemia (PHHI).
@article{Giugliano2000a,
author = {Giugliano, M},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1162/089976600300015646},
journal = {Neural Comput},
journal-full = {Neural computation},
mesh = {Algorithms; Computer Simulation; Markov Chains; Neural Conduction; Neural Networks, Computer; Neuronal Plasticity; Synapses},
month = apr,
number = {4},
pages = {903-31},
pmid = {10770837},
pst = {ppublish},
title = {Synthesis of generalized algorithms for the fast computation of synaptic conductances with Markov kinetic models in large network simulations},
volume = {12},
year = {2000},
bdsk-url-1 = {https://doi.org/10.1162/089976600300015646}
}
Markovkinetic models constitute a powerful framework to analyze patch-clamp data from single-channel recordings and model the dynamics of ion conductances and synaptic transmission between neurons. In particular, the accurate simulation of a large number of synaptic inputs in wide-scale network models may result in a computationally highly demanding process. We present a generalized consolidating algorithm to simulate efficiently a large number of synaptic inputs of the same kind (excitatory or inhibitory), converging on an isopotential compartment, independently modeling each synaptic current by a generic n-state Markov model characterized by piece-wise constant transition probabilities. We extend our findings to a class of simplified phenomenological descriptions of synaptic transmission that incorporate higher-order dynamics, such as short-term facilitation, depression, and synaptic plasticity.
@article{Giugliano:1999a,
author = {Giugliano, M and Bove, M and Grattarola, M},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1162/089976699300016296},
journal = {Neural Comput},
journal-full = {Neural computation},
mesh = {Algorithms; Computer Simulation; Models, Neurological; Neural Networks, Computer; Synaptic Transmission; Time Factors},
month = aug,
number = {6},
pages = {1413-26},
pmid = {10423501},
pst = {ppublish},
title = {Fast calculation of short-term depressing synaptic conductances},
volume = {11},
year = {1999},
bdsk-url-1 = {https://doi.org/10.1162/089976699300016296}
}
An efficient implementation of synaptic transmission models in realistic network simulations is an important theme of computational neuroscience. The amount of CPU time required to simulate synaptic interactions can increase as the square of the number of units of such networks, depending on the connectivity convergence. As a consequence, any realistic description of synaptic phenomena, incorporating biophysical details, is computationally highly demanding. We present a consolidating algorithm based on a biophysical extended model of ligand-gated postsynaptic channels, describing short-term plasticity such as synaptic depression. The considerable speed-up of simulation times makes this algorithm suitable for investigating emergent collective effects of short-term depression in large-scale networks of model neurons.
@article{Giugliano:1999,
author = {Giugliano, M and Bove, M and Grattarola, M},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1023/a:1008979302515},
journal = {J Comput Neurosci},
journal-full = {Journal of computational neuroscience},
mesh = {Action Potentials; Models, Neurological; Neurons; Nonlinear Dynamics; Signal Transduction; Synapses},
number = {3},
pages = {247-54},
pmid = {10596836},
pst = {ppublish},
title = {Activity-driven computational strategies of a dynamically regulated integrate-and-fire model neuron},
volume = {7},
year = {1999},
bdsk-url-1 = {https://doi.org/10.1023/a:1008979302515}
}
Activity-dependent slow biochemical regulation processes, affecting intrinsic properties of a neuron, might play an important role in determining information processing strategies in the nervous system. We introduce second-order biochemical phenomena into a linear leaky integrate-and-fire model neuron together with a detailed kinetic description for synaptic signal transduction. In this framework, we investigate the membrane intrinsic electrical properties differentiation, showing the appearance of activity-dependent shifts between integration and temporal coincidence detection operating mode, for the single unit of a network.
@article{Bove:1998,
author = {Bove, M and Martinoia, S and Verreschi, G and Giugliano, M and Grattarola, M},
date-added = {2023-12-26 22:08:18 +0100},
date-modified = {2023-12-26 22:08:18 +0100},
doi = {10.1016/s0956-5663(98)00015-3},
journal = {Biosens Bioelectron},
journal-full = {Biosensors \& bioelectronics},
mesh = {Animals; Cells, Cultured; Computer Simulation; Electric Stimulation; Ganglia, Spinal; Humans; Microelectrodes; Nerve Net; Stimulation, Chemical; Synaptic Transmission},
month = sep,
number = {6},
pages = {601-12},
pmid = {9828355},
pst = {ppublish},
title = {Analysis of the signals generated by networks of neurons coupled to planar arrays of microtransducers in simulated experiments},
volume = {13},
year = {1998},
bdsk-url-1 = {https://doi.org/10.1016/s0956-5663(98)00015-3}
}
Planar microelectrode arrays can be used to characterize the dynamics of networks of neurons reconstituted in vitro. In this paper simulations related to experiments of the electrical activity recording by means of planar arrays of microtransducers coupled to networks of neurons are described. First a detailed model of single and synaptically connected neurons is given, appropriate to computer simulate the action potentials of neuronal populations. Then ’realistic’ signals are generated. These signals are intended to reproduce, both in shape and intensity, those recorded by a microelectrode array. Typical experimental conditions are considered, and a detailed analysis given, of the bioelectronic coupling and of its influence on the shape of the recorded signals. Finally, simulated experiments dealing with dorsal root ganglia neurons are described and analysed in comparison with experimental results reported in the literature and obtained in our own laboratory. The effectiveness of the planar microelectrode technique is briefly discussed.
Michele GIUGLIANO
Professor of Bioengineering
University of Modena and Reggio Emilia
Dept. Biomedical, Metabolic & Neural Sciences
v. Campi 287
I-41125 Modena (Italy)
© 2024 Michele GIUGLIANO