GABA(B) receptor-activation inhibits GABAergic synaptic transmission in parvocellular neurones of rat hypothalamic paraventricular nucleus.
The paraventricular nucleus of the hypothalamus contains three classes of neurones: (i) magnocellular and (ii) parvocellular neurosecretory neurones and (iii) nonendocrine projection neurones. The present study aimed to determine whether functional GABA(B) receptors are present on axon terminals that synapse with parvocellular neurosecretory and nonendocrine paraventricular neurones and to determine how activation of GABA(B) receptors control GABAergic input to these neurones. Whole-cell recordings were performed in coronal hypothalamic slices of the rat containing the paraventricular nucleus. GABA(A) receptor-mediated inhibitory postsynaptic currents (i.p.s.c.) were isolated pharmacologically in the presence of antagonists of glutamatergic ionotropic receptors. We found that baclofen, an agonist of GABA(B) receptors, decreased the frequency of spontaneous and miniature i.p.s.c. It also decreased the amplitude of evoked i.p.s.c. These effects were suppressed by CGP55845A, a competitive antagonist of GABA(B) receptors. CGP55845A also increased the frequency of miniature i.p.s.c. and the amplitude of evoked i.p.s.c., suggesting that, in physiological conditions, presynaptic GABA(B) receptors exert a tonic inhibition on GABA release. Baclofen had no effect on GABA-evoked postsynaptic currents, suggesting that the baclofen-dependent suppression of GABAergic i.p.s.c. was exclusively due to a presynaptic action of the agonist. Our data indicate that GABA(B) receptors are present on axon terminals of GABAergic presynaptic neurones contacting parvocellular neurosecretory and nonendocrine paraventricular neurones, and suggest that GABA(B) receptors exert a tonic inhibition of GABA release from GABAergic terminals. Activation of these receptors causes disinhibition of parvocellular neurosecretory and nonendocrine paraventricular neurones.
Liu
X
X
Department of Basic Neuroscience, University Medical Centre, Geneva, Switzerland.
Tribollet
E
E
Raggenbass
M
M
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010721:Phosphinic Acids / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism; D009435:Synaptic Transmission
D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D018080:Receptors, GABA-B; C085075:CGP 55845A; D001418:Baclofen