Inhibitory Synaptic Potentials in Guinea-pig Substantia Nigra Dopamine Neurones in Vitro

Overview

Journal J Physiol

Specialty Physiology

Date 1994 Sep 15

PMID 7837097

Citations 20

Authors

M A Hausser

W H Yung

Affiliations

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Abstract

1. The properties of stimulus-evoked and spontaneous inhibitory synaptic potentials were examined in guinea-pig substantia nigra dopamine neurones in sagittal and coronal midbrain slices in the presence of glutamate 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, with peak latencies of about 30 and 250 ms, respectively. The fast component was sensitive to chloride injection, reversed polarity at -79.4 +/- 1.1 mV and was blocked by the GABAA receptor antagonists picrotoxin and bicuculline. The slow IPSP reversed at -99.3 +/- 5.4 mV and was blocked by the GABAB receptor antagonists 2-hydroxysaclofen and CGP 35348. 3. Spontaneous IPSPs were observed in many neurones. These events reversed polarity at -77.5 +/- 2.6 mV and were completely blocked by bicuculline and/or picrotoxin. In the presence of TTX, small spontaneous events remained which probably represent miniature IPSPs. In coronal slices, application of 4-aminopyridine raised the frequency of spontaneous IPSPs, presumably by activating nigral interneurones, but failed to reveal spontaneous biphasic IPSPs or spontaneous pure slow IPSPs. 4. The amplitude of the fast IPSPs fluctuated from trial to trial. Amplitude histograms of minimal fast IPSPs displayed evenly spaced peaks, 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 microM) showed paired-pulse facilitation. The GABAB agonist baclofen inhibited the fast IPSP via a presynaptic mechanism. The pharmacologically isolated slow IPSP showed marked paired-pulse facilitation. 6. It is concluded that synaptic inhibition in the substantia nigra is mediated by GABA, is relatively resistant to frequency-dependent depression and is regulated by presynaptic GABAB autoreceptors. Striatonigral and pallidonigral fibres activate both GABAA and GABAB receptors, while intranigral pathways appear to activate predominantly GABAA receptors.

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