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PMID: 7837097 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Inhibitory synaptic potentials in guinea-pig substantia nigra dopamine neurones in vitro.

The Journal of physiology ·Vol. 479 ( Pt 3) ·1994-09-15 ·Pages 401-22

Häusser MA, Yung WH

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.

MeSH Terms
Animals Dopamine/physiology Evoked Potentials/drug effects,physiology GABA Antagonists/pharmacology Globus Pallidus/cytology,physiology Guinea Pigs Immunohistochemistry In Vitro Techniques Microelectrodes Neural Pathways/cytology,physiology Neurons/drug effects,enzymology,physiology Receptors, Amino Acid/antagonists & inhibitors Receptors, GABA/drug effects Substantia Nigra/cytology,enzymology,physiology Synapses/drug effects,physiology Synaptic Membranes/drug effects,physiology Tyrosine 3-Monooxygenase/metabolism
Chemicals
GABA Antagonists Receptors, Amino Acid Receptors, GABA Tyrosine 3-Monooxygenase Dopamine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Häusser M A
University Laboratory of Physiology, Oxford.
Yung W H
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
Published
1994-09-15
Pages
401-22
Language
English
Region
England
NLM ID
0266262
PMCID
PMC1155759
Subset
IM
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