AREGU May 47/5

Cui, Lu-Ning, Elaine Coderre, and Leo P. Renaud. GABAB presynaptically modulates suprachiasmatic input to hypothalamic paraventricular magnocellular neurons. Am J Physiol Regulatory Integrative Comp Physiol 278: R1210– R1216, 2000.—This study used whole cell patch clamp recordings in rat hypothalamic slice preparations to evaluate the effects of GABAB receptor activation on GABAA-mediated inhibitory postsynaptic currents (IPSCs) in paraventricular nucleus magnocellular neurons evoked by electrical stimulation in the suprachiasmatic nucleus (SCN). Baclofen induced a dose-dependent (1–10 μM) and reversible reduction in SCN-evoked IPSC amplitude (11/11 cells), blockable with 2-hydroxysaclofen (300 μM; 3/3 cells). IPSCs displayed pairedpulse depression (PPD), attenuated by both baclofen and 2-hydroxysaclofen, but neither altered resting membrane conductances or IPSC time constants of decay. Baclofen induced a significant dose-dependent (1–100 μM) reduction in frequency, but not amplitude, of spontaneous IPSCs and miniature IPSCs, reversible with 2-hydroxysaclofen pretreatment. Baclofen effects and PPD persisted in slices pretreated with pertussis toxin (PTX) and N-ethylmaleimide, implying that these GABAB receptors are coupled to PTX-insensitive G proteins. Responses were unaltered by barium (2 mM) or nimodipine, ruling out involvement of K1 channels and L-type Ca21 channels. Thus preand postsynaptic GABAB and GABAA receptors participate in SCN entrainment of paraventricular neurosecretory neurons.