Chloride dynamics alter the input-output properties of neurons
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 r...
| 主要な著者: | , , , |
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| フォーマット: | Journal article |
| 言語: | English |
| 出版事項: |
Public Library of Science
2020
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| _version_ | 1826258266286456832 |
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| author | Currin, CB Trevelyan, AJ Akerman, CJ Raimondo, JV |
| author_facet | Currin, CB Trevelyan, AJ Akerman, CJ Raimondo, JV |
| author_sort | Currin, CB |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:31:15Z |
| format | Journal article |
| id | oxford-uuid:09b865bb-2524-43ea-969c-06ddea9d4f4f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:31:15Z |
| publishDate | 2020 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:09b865bb-2524-43ea-969c-06ddea9d4f4f2022-03-26T09:19:54ZChloride dynamics alter the input-output properties of neuronsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:09b865bb-2524-43ea-969c-06ddea9d4f4fEnglishSymplectic ElementsPublic Library of Science2020Currin, CBTrevelyan, AJAkerman, CJRaimondo, JVFast 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. |
| spellingShingle | Currin, CB Trevelyan, AJ Akerman, CJ Raimondo, JV Chloride dynamics alter the input-output properties of neurons |
| title | Chloride dynamics alter the input-output properties of neurons |
| title_full | Chloride dynamics alter the input-output properties of neurons |
| title_fullStr | Chloride dynamics alter the input-output properties of neurons |
| title_full_unstemmed | Chloride dynamics alter the input-output properties of neurons |
| title_short | Chloride dynamics alter the input-output properties of neurons |
| title_sort | chloride dynamics alter the input output properties of neurons |
| work_keys_str_mv | AT currincb chloridedynamicsaltertheinputoutputpropertiesofneurons AT trevelyanaj chloridedynamicsaltertheinputoutputpropertiesofneurons AT akermancj chloridedynamicsaltertheinputoutputpropertiesofneurons AT raimondojv chloridedynamicsaltertheinputoutputpropertiesofneurons |