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 GABA(A)-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 microM) and reversible reduction in SCN-evoked IPSC amplitude (11/11 cells), blockable with 2-hydroxysaclofen (300 microM; 3/3 cells). IPSCs displayed paired-pulse 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 microM) 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 GABA(B) receptors are coupled to PTX-insensitive G proteins. Responses were unaltered by barium (2 mM) or nimodipine, ruling out involvement of K(+) channels and L-type Ca(2+) channels. Thus pre- and postsynaptic GABA(B) and GABA(A) receptors participate in SCN entrainment of paraventricular neurosecretory neurons.
Cui
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LN
Laboratory of Neurosciences, Loeb Health Research Institute, Ottawa Hospital Civic Site; and University of Ottawa, Ottawa, Ontario, Canada K1Y 4E9.
Coderre
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E
Renaud
L P
LP
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D004558:Electric Stimulation; D005033:Ethylmaleimide / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009474:Neurons / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D018755:GABA Agonists; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D001418:Baclofen; D005033:Ethylmaleimide; C057491:2-hydroxysaclofen