Probing the polarity of spontaneous perisomatic GABAergic synaptic transmission in the mouse CA3 circuit invivo.

Abstract

The hypothesis that reversed, excitatory GABA may be involved in various brain pathologies, including epileptogenesis, is appealing but controversial because of the technical difficulty of probing endogenous GABAergic synaptic function invivo. We overcome this challenge by non-invasive extracellular recording of neuronal firing responses to optogenetically evoked and spontaneously occurring inhibitory perisomatic GABAergic field potentials, generated by individual parvalbumin interneurons on their target pyramidal cells. Our direct probing of GABAergic transmission suggests a rather anecdotal participation of excitatory GABA in two specific models of epileptogenesis in the mouse CA3 circuit invivo, even though this does not preclude its expression in other brain areas or pathological conditions. Our approach allows the detection of distinct alterations of inhibition during spontaneous activity invivo, with high sensitivity. It represents a promising tool for the investigation of excitatory GABA in different pathological conditions that may affect the hippocampal circuit.