GABA(B) RECEPTORS PRESYNAPTICALLY MODULATE EXCITATORY SYNAPTIC TRANSMISSION IN THE RAT SUPRAOPTIC NUCLEUS IN-VITRO

1. The effect of gamma-aminobutyric acid-B (GABA(B))-receptor activati on on excitatory synaptic transmission in the rat supraoptic nucleus ( SON) was examined using the nystatin perforated-patch whole cell recor ding technique in coronal hypothalamic slices. 2. Stimulationof the hy pothalamic region dorso-medial to the SON elicited glutamate and GABAA -receptor-mediated synaptic responses in electrophysiologically identi fied magnocellular neurosecretory cells. 3. Bath application of the GA BA(B)-receptor agonist, +/-baclofen reversibly reduced pharmacological ly isolated, glutamate-mediated excitatory postsynaptic currents (EPSC s) in a concentration-dependent manner. At the concentrations used, ba clofen altered neither the postsynaptic conductances of these cells no r their response to bath applied lpha-amino-3-hydroxy-5-methylisoxazol e-4-propionic acid (AMPA). 4. The baclofen-induced synaptic depression was accompanied by an increase in paired pulse facilitation (PPF). Th is increase in PPF, as well as the synaptic depression, was blocked by the GABA(B) receptor antagonists CGP36742 and saclofen. 5. In additio n to blocking the actions of baclofen in this nucleus, CGP36742 caused an increase in the evoked EPSC amplitude without altering postsynapti c cell conductances or responses induced by bath-applied AMPA. Contrar y to the action of CGP36742, saclofen caused a baclofen-like depressio n of the evoked EPSC, suggesting that it may act as a partial GABA(B) receptor agonist. 6. These results indicate that the activation of pre synaptic GABA(B) receptors reduces fast excitatory synaptic transmissi on in the SON. They further suggest that presynaptic GABA(B) receptors may be tonically activated in vitro. Thus GABA(B) receptors may influ ence the level of activity and excitation of SON neurons and hence mod ulate the secretion of the regulatory neuropeptides vasopressin and ox ytocin.