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Chloride dynamics alter the input-output properties of neurons

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.

Publication metadata

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


DOI: 10.1371/journal.pcbi.1007932

PubMed id: 32453795


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