Abstract
In vitro studies have reported high intracellular chloride levels, depolarizing and potentially excitatory actions of GABA in various pathological conditions. Consequently, great expectations are now pinned on drugs potentially restoring low [Cl−]i as novel therapies for a wide range of brain disorders. However, the clinical relevance of this hypothesis remains largely speculative because of the yet unresolved technical difficulty to evaluate the polarity of GABAergic transmission in vivo. Here, we show that the polarity of GABAergic transmission can be probed across the CA3 hippocampal circuit in vivo with single cell resolution, by combining extracellular detection of unitary inhibitory postsynaptic field-potentials (fIPSPs) and silicon probe recording of the firing activity of multiple individually identified neurons. As an example application, we provide direct evidence for depolarizing actions of perisomatic GABAergic transmission and time-locked excitation of CA3 pyramidal neurons in acute and chronic mouse models of epilepsy.