GABAergic input to cholinergic nucleus basalis neurons

A. Khateb, P. Fort, S. Williams, M. Serafin, M. Mühlethaler, B. E. Jones

Research output: Contribution to journalArticlepeer-review

Abstract

The potential influence of GABAergic input to cholinergic basalis neurons was studied in guinea-pig basal forebrain slices. GABA and its agonists were applied to electrophysiologically-identified cholinergic neurons, of which some were labelled with biocytin and confirmed to be choline acetyltransferase-immunoreactive. Immunohistochemistry for glutamate decarboxylase was also performed in some slices and revealed GABAergic varicosities in the vicinity of the biocytin-filled soma and dendrites of electrophysiologically-identified cholinergic cells. From rest (average - 63 mV), the cholinergic cells were depolarized by GABA. The depolarization was associated with a decrease in membrane resistance and diminution in firing. The effect was mimicked by muscimol, the specific agonist for GABA(A) receptors, and not by baclofen, the specific agonist for GABA(B) receptors, which had no discernible effect. The GABA- and muscimol-evoked depolarization and decrease in resistance were found to be postsynaptic since they persisted in the presence of solutions containing either high Mg2+/low Ca2+ or tetrodotoxin. They were confirmed as being mediated by a GABA(A) receptor, since they were antagonized by bicuculline. The reversal potential for the muscimol effect was estimated to be ~ -45 mV, which was - 15 mV above the resting membrane potential. Finally, in some cholinergic cells, spontaneous subthreshold depolarizing synaptic potentials (average 5 mV in amplitude), which were rarely associated with action potentials, were recorded and found to persist in the presence of glutamate receptor antagonists but to be eliminated by bicuculline. These results suggest that GABAergic input may be depolarizing, yet predominantly inhibitory to cholinergic basalis neurons.

Original languageEnglish
Pages (from-to)937-947
Number of pages11
JournalNeuroscience
Volume86
Issue number3
DOIs
StatePublished - 8 Jun 1998
Externally publishedYes

Bibliographical note

Funding Information:
We thank Lynda Mainville and Daniele Machard for their excellent technical assistance. This work was supported by grants from the Swiss Fonds National, the Sandoz and Roche Foundations to MM and the Canadian Medical Research Council (MRC) to BEJ. PF was supported by fellowships from Fondation Fyssen and Fondation pour la Recherche Médicale (FRM); SW was the recipient of a post-doctoral fellowship from the Canadian MRC.

Keywords

  • Basal forebrain
  • Choline acetyltransferase
  • GABA(A) receptors
  • Glutamate decarboxylase
  • Muscimol
  • Sleep-wake states

ASJC Scopus subject areas

  • Neuroscience (all)

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