title: GABA(B) presynaptically modulates suprachiasmatic input to hypothalamic paraventricular magnocellular neurons.
abstract: 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.
authors.affiliation: Laboratory of Neurosciences, Loeb Health Research Institute, Ottawa Hospital Civic Site; and University of Ottawa, Ottawa, Ontario, Canada K1Y 4E9.
authors.forename: L N
authors.initials: LN
authors.lastname: Cui
authors.forename: E
authors.initials: E
authors.lastname: Coderre
authors.forename: L P
authors.initials: LP
authors.lastname: Renaud
mesh_terms: 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
chemical_list: 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