Active cortical networks promote shunting fast synaptic inhibitionin vivo

Fast synaptic inhibition determines neuronal response properties in the mammalian brain and is mediated by chloride-permeable ionotropic GABA-A receptors (GABA A Rs). Despite their fundamental role, it is still not known how GABA A Rs signal in the intact brain. Here we use in vivo gramicidin recordings to investigate synaptic GABA A R signaling in mouse cortical pyramidal neurons under conditions that preserve native transmembrane chloride gradients. In anaesthetized cortex, synaptic GABA A Rs exert classic hyperpolarizing effects. In contrast, GABA A R-mediated synaptic signaling in awake cortex is found to be predominantly shunting. This is due to more depolarized GABA A R equilibrium potentials (E GABAAR ), which are shown to result from the high levels of synaptic activity that characterize awake cortical networks. The E GABAAR 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 GABA A R signaling adapts to optimize cortical functions.