ENHANCEMENT OF GABA-MEDIATED INHIBITION OF RAT MEDIAL VESTIBULAR NUCLEUS NEURONS BY THE NEUROSTEROID 20-HYDROXYECDYSONE

In vivo electrophysiological and patch-clamp studies were performed to determine whether 20-hydroxyecdysone (20-HE), a neurosteroid, influen ced neuronal activities of the medial vestibular nucleus (MVN) using c hloral hydrate-anesthetized rats and dissociated MVN neurons, respecti vely. Single neuronal activities of MVN were extracellularly recorded with a glass-insulated silver wire microelectrode attached along a sev en-barreled micropipette. Each micropipette was filled with 20-HE, glu tamate, bicuculline or 2 M NaCl. These chemicals were applied microion tophoretically to the immediate vicinity of the target neurons. Microi ontophoretically applied 20-HE (20-80 nA) dose-dependently decreased r otation-induced firings of both type I and II neurons, which were iden tified according to their responses to horizontal sinusoidal rotations . Microiontophoretically applied bicuculline, a GABA(A) receptor antag onist, inhibited 20-HE-induced decreases in neuronal firing of MVN. Th ese findings suggest that 20-HE potentiates the action of GABA, probab ly by acting directly on the GABA(A) receptor of MVN neurons. In addit ion, microiontophoretically applied 20-HE decreased firings induced by glutamate in both type I and II neurons. This decrease by 20-HE was a lso antagonized with bicuculline. Furthermore, the effects of 20-HE on GABA-induced currents in acutely dissociated MVN neurons were investi gated using the whole-cell patch-clamp technique. Under voltage-clamp conditions, GABA (10 mu M)-induced currents were potentiated in the pr esence of 20-HE (100 mu M). These findings suggest that 20-HE inhibits MVN neurons by acting on the modulatory site on GABA receptor-ion cha nnel complexes to potentiate GABA inhibition.