INHIBITORY SYNAPTIC POTENTIALS IN GUINEA-PIG SUBSTANTIA-NIGRA DOPAMINE NEURONS IN-VITRO

1. The properties of stimulus-evoked and spontaneous inhibitory synapt ic potentials were examined in guinea-pig substantia nigra dopamine ne urones in sagittal and coronal midbrain slices in the presence of glut amate receptor antagonists. 2. Focal electrical stimulation within the substantia nigra, cerebral peduncle, internal capsule or the striatum evoked a biphasic IPSP consisting of a fast and a slow component, wit h peak latencies of about 30 and 250 ms, respectively. The fast compon ent was sensitive to chloride injection, reversed polarity at -79.4 +/ - 1.1 mV and was blocked by the GABA(A) receptor antagonists picrotoxi n and bicuculline. The slow IPSP reversed at -99.3 +/- 5.4 mV and was blocked by the GABA(B) receptor antagonists 2-hydroxysaclofen and CGP 35348. 3. Spontaneous IPSPs were observed in many neurones. These even ts reversed polarity at -77.5 +/- 2.6 mV and were completely blocked b y bicuculline and/or picrotoxin. In the presence of TTX, small spontan eous events remained which probably represent miniature IPSPs. In coro nal slices, application of 4-aminopyridine raised the frequency of spo ntaneous IPSPs, presumably by activating nigral interneurones, but fai led to reveal spontaneous biphasic IPSPs or spontaneous pure slow IPSP s. 4. The amplitude of the fast IPSPs fluctuated from trial to trial. Amplitude histograms of minimal fast IPSPs displayed evenly spaced pea ks, suggesting that synaptic transmission is quantal at these synapses . The measured peak spacing depended on the driving force for Cl-. 5. The fast IPSP showed little or no paired-pulse depression, and in the presence of 2-hydroxysaclofen (400-600 mu M) showed paired-pulse facil itation. The GABA(B) agonist baclofen inhibited the fast IPSP via a pr esynaptic mechanism. The pharmacologically isolated slow IPSP showed m arked paired-pulse facilitation. 6. It is concluded that synaptic inhi bition in the substantia nigra is mediated by GABA, is relatively resi stant to frequency-dependent depression and is regulated by presynapti c GABA(B) autoreceptors. Striatonigral and pallidonigral fibres activa te both GABA(A) and GABA(B) receptors, while intranigral pathways appe ar to activate predominantly GABA(A) receptors.