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Chloride dynamics alter the input-output properties of neurons

Currin, Christopher B ; Trevelyan, Andrew J ; Akerman, Colin J ; Raimondo, Joseph V Berry, Hugues

PLoS computational biology, 2020-05, Vol.16 (5), p.e1007932-e1007932 [Periódico revisado por pares]

United States: Public Library of Science

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Chloride dynamics alter the input-output properties of neurons
Autor: Currin, Christopher B ; Trevelyan, Andrew J ; Akerman, Colin J ; Raimondo, Joseph V
Berry, Hugues
Assuntos: Action Potentials ; Animals ; Biology ; Biology and Life Sciences ; Brain - physiology ; Chloride ; Chloride currents ; Chlorides ; Chlorides - chemistry ; Computational biology ; Computational neuroscience ; Computer Simulation ; Dendrites - physiology ; Dichloropropane ; Dynamics ; Extrusion ; Health sciences ; Hippocampus - physiology ; Homeostasis ; Humans ; Infectious diseases ; Inhibition ; Kinetics ; Male ; Medicine and Health Sciences ; Methods ; Models, Neurological ; Neurons ; Neurons - physiology ; Neurosciences ; Organ Culture Techniques ; Physical Sciences ; Physiological aspects ; Protein Binding ; Pyramidal Cells - physiology ; Rats ; Rats, Wistar ; Receptors ; Receptors, GABA - physiology ; Receptors, GABA-A - physiology ; Research and Analysis Methods ; Supervision ; Synapses ; Synapses - physiology ; γ-Aminobutyric acid ; γ-Aminobutyric acid receptors
É parte de: PLoS computational biology, 2020-05, Vol.16 (5), p.e1007932-e1007932
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The authors have declared that no competing interests exist.
Descrição: 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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Chloride dynamics alter the input-output properties of neurons

Currin, Christopher B ; Trevelyan, Andrew J ; Akerman, Colin J ; Raimondo, Joseph V Berry, Hugues

United States: Public Library of Science

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