GABA(B)-receptor-mediated control of GABAergic inhibition in rat histaminergic neurons in vitro

The onset of slow wave sleep may require an inhibition of histaminergic neu rons by GABAergic afferents from the ventrolateral preoptic area. We have u tilized electrophysiological methods in an in vitro brain slice preparation to examine the role of GABA(B) receptor activation in GABAergic synaptic i nhibition in histaminergic neurons of the tuberomammillary nucleus. Tetrodo toxin blocked evoked GABAergic IPSPs but not miniature IPSPs or IPSCs. Evok ed IPSPs varied in amplitude and exhibited failures of transmission. Baclof en reduced the amplitude of evoked IPSPs in all experiments and often cause d an increase in failures of transmission. Responses elicited by applicatio n of exogenous GABA were insensitive to baclofen treatment. The action of b aclofen was blocked by CGP-35348 (100 mu M), a GABA(B) receptor antagonist, which also enhanced the amplitude of evoked IPSPs. The frequency of sponta neous and miniature IPSPs and IPSCs was reduced by baclofen. However, the a mplitude distribution of mIPSCs was not altered. We conclude that GABA rele ase onto TM neurons is under presynaptic control via GABA(B) receptors. Thi s presynaptic control of transmission to tuberomammillary neurons may reduc e inhibition, increasing histamine release and enhancing wakefulness.