GABA(B) presynaptically modulates suprachiasmatic input to hypothalamic paraventricular magnocellular neurons

This study used whole cell patch clamp recordings in rat hypothalamic slice preparations to evaluate the effects of GABA(B) receptor activation on GAB A(A)-mediated inhibitory postsynaptic currents (IPSCs) in paraventricular n ucleus magnocellular neurons evoked by electrical stimulation in the suprac hiasmatic nucleus (SCN). Baclofen induced a dose-dependent (1-10 mu M) and reversible reduction in SCN-evoked IPSC amplitude (11/11 cells), blockable with 2-hydroxysaclofen (300 mu M; 3/3 cells). IPSCs displayed paired-pulse depression (PPD), attenuated by both baclofen and 2-hydroxysaclofen, but ne ither altered resting membrane conductances or IPSC time constants of decay . Baclofen induced a significant dose-dependent (1-100 mu M) reduction in f requency, but not amplitude, of spontaneous IPSCs and miniature IPSCs, reve rsible with 2-hydroxysaclofen pretreatment. Baclofen effects and PPD persis ted in slices pretreated with pertussis toxin (PTX) and N-ethylmaleimide, i mplying that these GABA(B) receptors are coupled to PTX-insensitive G prote ins. Responses were unaltered by barium (2 mM) or nimodipine, ruling out in volvement of K+ channels and L-type Ca2+ channels. Thus pre- and postsynapt ic GABA(B) and GABA(A) receptors participate in SCN entrainment of paravent ricular neurosecretory neurons.