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Computational Modeling of Inhibitory Transsynaptic Signaling in Hippocampal and Cortical Neurons Expressing Intrabodies Against Gephyrin. | LitMetric

AI Article Synopsis

  • GABAergic transmission is essential for regulating neuronal activity and is linked to cognitive functions, with the scaffold protein gephyrin playing a crucial role in anchoring GABA receptors at synapses.
  • The balance between excitation and inhibition (E/I balance) is vital for proper brain function, and disruptions in this balance can lead to disorders like epilepsy and schizophrenia.
  • The article utilizes a computational model to analyze how blocking gephyrin affects inhibitory postsynaptic currents (IPSCs) and suggests methods for correlating experimental changes in synaptic events with underlying cellular pathways.

Article Abstract

GABAergic transmission regulates neuronal excitability, dendritic integration of synaptic signals and oscillatory activity, thought to be involved in high cognitive functions. By anchoring synaptic receptors just opposite to release sites, the scaffold protein gephyrin plays a key role in these tasks. In addition, by regulating GABA receptor trafficking, gephyrin contributes to maintain, at the network level, an appropriate balance between Excitation (E) and Inhibition (I), crucial for information processing. An E/I imbalance leads to neuropsychiatric disorders such as epilepsy, schizophrenia and autism. In this article, we exploit a previously published computational method to fit spontaneous synaptic events, using a simplified model of the subcellular pathways involving gephyrin at inhibitory synapses. The model was used to analyze experimental data recorded under different conditions, with the main goal to gain insights on the possible consequences of gephyrin block on IPSCs. The same approach can be useful, in general, to analyze experiments designed to block a single protein. The results suggested possible ways to correlate the changes observed in the amplitude and time course of individual events recorded after different experimental protocols with the changes that may occur in the main subcellular pathways involved in gephyrin-dependent transsynaptic signaling.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309579PMC
http://dx.doi.org/10.3389/fncel.2020.00173DOI Listing

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