Endogenous GABA Release Inhibits the Firing of Adult Gonadotropin-Releasing Hormone Neurons

Abstract

Abstract The effect of endogenous γ-aminobutyric acid (GABA)A receptor-mediated signaling on the excitability of adult male and female GnRH neurons was examined using gramicidin perforated-patch electrophysiology in GnRH-LacZ and GnRH-GFP (green fluorescent protein) transgenic mouse models. In both lines of mice, approximately 80% of GnRH neurons (n = 42) responded to the selective GABAA receptor antagonist bicuculline (20 μm) with a rapid and reversible membrane depolarization and/or increase in firing rate. Approximately 16% of GnRH neurons gave no response, and two neurons were inhibited by bicuculline. The same depolarizing responses (78%) were obtained from adult gonadectomized GnRH-GFP mice. The depolarizing response to bicuculline persisted in the presence of tetrodotoxin, demonstrating that even action potential-independent GABA release was acting to reduce GnRH neuron membrane potential. These observations show that endogenous GABA signaling through the GABAA receptor exerts a powerful net inhibitory effect upon the excitability of mature GnRH neurons.