Photopotentiation of the GABA _A receptor with caged diazepam

Abstract

Significance Anxiety, autism, epilepsy, and schizophrenia are just a few of the critical conditions associated with a dysfunctional γ-aminobutyric acid–ergic (GABAergic) system. Interrogation of such transmission is thus of ultimate importance for a better pathophysiological characterization of defective neuronal populations and proper treatment development. We describe here a probing mode designed to interrogate the GABAergic transmission. Specifically, we harnessed the photosensitive nature of a photoactivatable version of diazepam to specifically modulate the GABA type A (GABA A ) receptor kinetics upon photoirradiation. This technology allows the potentiation of GABAergic currents without affecting the receptor activation event operated by endogenous GABA. The important functional advance sets the basis for a specific explorative approach to investigate the pathological roles of GABA A .