GABA(B) RECEPTOR-MEDIATED INHIBITION OF SPONTANEOUS INHIBITORY SYNAPTIC CURRENTS IN RAT MIDBRAIN CULTURE

1. Tight-seal, whole-cell recording was used to study GABA(B) receptor -mediated inhibition of spontaneous inhibitory synaptic currents in cu ltured rat midbrain neurones. 2. Spontaneous miniature inhibitory post synaptic currents (mIPSCs) were recorded in tetrodotoxin (TTX), Cd2+ a nd Ba2+. (R)-(-)-baclofen reduced the frequency of mIPSCs through a pr esynaptic mechanism. The EC50 for this effect was 7 mu M. It was antag onized by the GABA(B) receptor antagonist CGP55845A (0.5 mu M.3. In pe rtussis toxin (PTX)-treated cultures, some GABA(B) receptor-mediated r eduction of the frequency of mTPSCs persisted. In contrast, PTX treatm ent totally abolished inhibition of miniature excitatory postsynaptic currents (mEPSCs). 4. In PTX-treated cultures, a saturating concentrat ion of (R)-(-)-baclofen inhibited action potential-generated IPSCs but not EPSCs. 5. PTX treatment abolished the (R)-)-baclofen-mediated inh ibition of high voltage-activated somatic Ca2+ currents and of spontan eous IPSCs depending on presynaptic Ca2+ entry. 6. We conclude that ce llular mechanisms underlying GABA(B) receptor-mediated inhibition of m IPSCs contribute to auto-inhibition of GABA release.