Presynaptic GABA_A receptors modulate thalamocortical inputs in layer 4 of Rat V1

Fast inhibitory GABAergic transmission plays a fundamental role in neural circuits. Current theories of cortical function assume that fast GABAergic inhibition acts via GABA_A receptors on postsynaptic neurons, while presynaptic effects of GABA depend on GABA B receptor activation. Manipulations of GABA_A receptor activity in vivo produced different effects on cortical function, which were generally ascribed to the mode of action of a drug, more than its site of action. Here we show that in rodent primary visual cortex, α4-containing GABA_A receptors can be located on subsets of glutamatergic and GABAergic presynaptic terminals and decrease synaptic transmission. Our data provide a novel mechanistic insight into the effects of changes in cortical inhibition; the ability to modulate inputs onto cortical circuits locally, via presynaptic regulation of release by GABA_A receptors.