Presynaptic GABA(B) receptors modulate organum vasculosum lamina terminalis-evoked postsynaptic currents in rat hypothalamic supraoptic neurons.
Whole-cell patch-clamp recordings obtained from 36 hypothalamic supraoptic nucleus neurons in explant preparations evaluated a role for GABA(B) receptors in modulating postsynaptic inhibitory and excitatory currents evoked by electrical stimulation in the organum vasculosum of the lamina terminalis. At a holding current of -65 mV, application of baclofen (1-10 microM) induced a dose-dependent reduction in the amplitude of pharmacologically isolated inhibitory and excitatory postsynaptic currents, converted paired-pulse depression in inhibitory postsynaptic currents to paired-pulse facilitation, and enhanced paired-pulse ratios for excitatory postsynaptic currents. In media containing 2-hydroxysaclofen (200-400 microM), baclofen-associated events were blocked and paired-pulse depression in evoked inhibitory postsynaptic currents was abolished. In addition, a progressive increase in the amplitude of inhibitory postsynaptic currents implied that GABA was endogenously active at presynaptic GABA(B) receptors. In contrast, no paired-pulse depression was observed for inhibitory postsynaptic currents evoked in six non-magnocellular neurons. Neither baclofen nor 2-hydroxysaclofen altered holding currents or input resistances in supraoptic neurons, or altered the kinetics of the evoked responses.These observations imply that the terminals of both inhibitory (GABAergic) and excitatory (glutamatergic) afferents to supraoptic nucleus neurons from organum vasculosum lamina terminalis neurons are subject to modulation by presynaptic GABA(B) receptors, and that this modulation is preferentially directed to the inhibitory inputs.
Kolaj
M
M
Neurosciences, Loeb Health Research Institute, Ottawa Hospital and University of Ottawa, Ontario, K1Y 4E9, Ottawa, Canada.
Yang
C R
CR
Renaud
L P
LP
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D018080:Receptors, GABA-B / Q000378:metabolism*; D013495:Supraoptic Nucleus / Q000502:physiology*; D014882:Water-Electrolyte Balance / Q000502:physiology*
D018755:GABA Agonists; D018756:GABA Antagonists; D018080:Receptors, GABA-B; D001418:Baclofen; C057491:2-hydroxysaclofen