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Lookup NU author(s): Professor Andrew Trevelyan
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2020 Currin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Fast synaptic inhibition is a critical determinant of neuronal output, with subcellular targeting of synaptic inhibition able to exert different transformations of the neuronal input-output function. At the receptor level, synaptic inhibition is primarily mediated by chloride-permeable Type A GABA receptors. Consequently, dynamics in the neuronal chloride concentration can alter the functional properties of inhibitory synapses. How differences in the spatial targeting of inhibitory synapses interact with intracellular chloride dynamics to modulate the input-output function of neurons is not well understood. To address this, we developed computational models of multi-compartment neurons that incorporate experimentally parametrised mechanisms to account for neuronal chloride influx, diffusion, and extrusion. We found that synaptic input (either excitatory, inhibitory, or both) can lead to subcellular variations in chloride concentration, despite a uniform distribution of chloride extrusion mechanisms. Accounting for chloride changes resulted in substantial alterations in the neuronal input-output function. This was particularly the case for peripherally targeted dendritic inhibition where dynamic chloride compromised the ability of inhibition to offset neuronal input-output curves. Our simulations revealed that progressive changes in chloride concentration mean that the neuronal input-output function is not static but varies significantly as a function of the duration of synaptic drive. Finally, we found that the observed effects of dynamic chloride on neuronal output were mediated by changes in the dendritic reversal potential for GABA. Our findings provide a framework for understanding the computational effects of chloride dynamics on dendritically targeted synaptic inhibition.
Author(s): Currin CB, Trevelyan AJ, Akerman CJ, Raimondo JV
Publication type: Article
Publication status: Published
Journal: PLoS Computational Biology
Year: 2020
Volume: 16
Issue: 5
Online publication date: 26/05/2020
Acceptance date: 06/05/2020
Date deposited: 23/06/2020
ISSN (print): 1553-734X
ISSN (electronic): 1553-7358
Publisher: Public Library of Science
URL: https://doi.org/10.1371/journal.pcbi.1007932
DOI: 10.1371/journal.pcbi.1007932
PubMed id: 32453795
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