Active cortical networks promote shunting fast synaptic inhibition in vivo

Burman, R. J.; Brodersen, P. J. N.; Raimondo, J. V.; Sen, A.; Akerman, C. J.

doi:10.1101/2023.03.01.530641

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bioRxiv · 10.1101/2023.03.01.530641

Active cortical networks promote shunting fast synaptic inhibition in vivo

Burman, R. J.·Brodersen, P. J. N.·Raimondo, J. V.·Sen, A.·Akerman, C. J.

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Abstract

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 anaesthetized 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. The EGABAAR observed in awake cortex can facilitate the decoupling of local networks, which improves the ability of the network to discriminate stimuli. Our findings therefore suggest that GABAAR signaling adapts to optimize cortical functions.

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Burman, R. J., Brodersen, P. J. N., Raimondo, J. V., Sen, A., Akerman, C. J.. 2023-03-02. Active cortical networks promote shunting fast synaptic inhibition in vivo. https://doi.org/10.1101/2023.03.01.530641

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