Active cortical networks promote shunting fast synaptic inhibition in vivo
Fast synaptic inhibition determines neuronal response properties in the mammalian brain and is mediated by chloride-permeable ionotropic GABA-A receptors (GABAARs). Despite their fundamental role, it is still not known how GABAARs signal in the intact brain. Here, we use in vivo gramicidin recording...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2023
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| _version_ | 1826312949400076288 |
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| author | Burman, RJ Brodersen, PJN Raimondo, JV Sen, A Akerman, CJ |
| author_facet | Burman, RJ Brodersen, PJN Raimondo, JV Sen, A Akerman, CJ |
| author_sort | Burman, RJ |
| collection | OXFORD |
| description | Fast synaptic inhibition determines neuronal response properties in the mammalian brain and is mediated by chloride-permeable ionotropic GABA-A receptors (GABAARs). Despite their fundamental role, it is still not known how GABAARs signal in the intact brain. Here, we use in vivo gramicidin recordings to investigate synaptic GABAAR signaling in mouse cortical pyramidal neurons under conditions that preserve native transmembrane chloride gradients. In anesthetized cortex, synaptic GABAARs exert classic hyperpolarizing effects. In contrast, GABAAR-mediated synaptic signaling in awake cortex is found to be predominantly shunting. This is due to more depolarized GABAAR equilibrium potentials (EGABAAR), which are shown to result from the high levels of synaptic activity that characterize awake cortical networks. Synaptic EGABAAR observed in awake cortex facilitates the desynchronizing effects of inhibitory inputs upon local networks, which increases the flexibility of spiking responses to external inputs. Our findings therefore suggest that GABAAR signaling adapts to optimize cortical functions. |
| first_indexed | 2024-03-07T08:07:54Z |
| format | Journal article |
| id | oxford-uuid:42b17977-27ad-4801-98b1-e52eedb2e84a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:03:19Z |
| publishDate | 2023 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:42b17977-27ad-4801-98b1-e52eedb2e84a2024-05-14T08:42:36ZActive cortical networks promote shunting fast synaptic inhibition in vivoJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:42b17977-27ad-4801-98b1-e52eedb2e84aEnglishSymplectic ElementsCell Press2023Burman, RJBrodersen, PJNRaimondo, JVSen, AAkerman, CJFast synaptic inhibition determines neuronal response properties in the mammalian brain and is mediated by chloride-permeable ionotropic GABA-A receptors (GABAARs). Despite their fundamental role, it is still not known how GABAARs signal in the intact brain. Here, we use in vivo gramicidin recordings to investigate synaptic GABAAR signaling in mouse cortical pyramidal neurons under conditions that preserve native transmembrane chloride gradients. In anesthetized cortex, synaptic GABAARs exert classic hyperpolarizing effects. In contrast, GABAAR-mediated synaptic signaling in awake cortex is found to be predominantly shunting. This is due to more depolarized GABAAR equilibrium potentials (EGABAAR), which are shown to result from the high levels of synaptic activity that characterize awake cortical networks. Synaptic EGABAAR observed in awake cortex facilitates the desynchronizing effects of inhibitory inputs upon local networks, which increases the flexibility of spiking responses to external inputs. Our findings therefore suggest that GABAAR signaling adapts to optimize cortical functions. |
| spellingShingle | Burman, RJ Brodersen, PJN Raimondo, JV Sen, A Akerman, CJ Active cortical networks promote shunting fast synaptic inhibition in vivo |
| title | Active cortical networks promote shunting fast synaptic inhibition in vivo |
| title_full | Active cortical networks promote shunting fast synaptic inhibition in vivo |
| title_fullStr | Active cortical networks promote shunting fast synaptic inhibition in vivo |
| title_full_unstemmed | Active cortical networks promote shunting fast synaptic inhibition in vivo |
| title_short | Active cortical networks promote shunting fast synaptic inhibition in vivo |
| title_sort | active cortical networks promote shunting fast synaptic inhibition in vivo |
| work_keys_str_mv | AT burmanrj activecorticalnetworkspromoteshuntingfastsynapticinhibitioninvivo AT brodersenpjn activecorticalnetworkspromoteshuntingfastsynapticinhibitioninvivo AT raimondojv activecorticalnetworkspromoteshuntingfastsynapticinhibitioninvivo AT sena activecorticalnetworkspromoteshuntingfastsynapticinhibitioninvivo AT akermancj activecorticalnetworkspromoteshuntingfastsynapticinhibitioninvivo |