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Computational modeling of inhibitory transsynaptic signaling in hippocampal and cortical neurons expressing intrabodies against gephyrin

Authors: Lupascu CA1, Morabito A2, Ruggeri F2, Parisi C2, Pimpinella D2, Pizzarelli R2, Meli G2, Marinelli S2, Cherubini E2, Cattaneo A2, and Migliore M1

Author information: 1Institute of Biophysics, National Research Council, Palermo, Italy, 2 European Brain Research Institute, Rome, Italy.

Corresponding author: Author (Lupascu CA carmen.lupascu@pa.ibf.cnr.it )

Journal: Frontiers in Cellular Neuroscience

Download Url: https://www.frontiersin.org/articles/10.3389/fncel.2020.00173/abstract

Citation: Lupascu CA, Morabito A, Ruggeri F, Parisi C, Pimpinella D, Pizzarelli R, Meli G, Marinelli S, Cherubini E, Cattaneo A & Migliore M (2020). Computational modeling of inhibitory transsynaptic signaling in hippocampal and cortical neurons expressing intrabodies against gephyrin. Frontiers in Celllular Neuroscience, In press.

Licence: the Creative Commons Attribution (CC BY) license  applies for all files. Under this Open Access license anyone  may copy, distribute, or reuse the files as long as the authors and the original source are properly cited.

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 GABAA 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 paper, 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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