Modulation of cholinergic nucleus basalis neurons by acetylcholine and n-methyl-d-aspartate

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

Research output: Contribution to journalArticlepeer-review


Known to exert an important modulatory influence on the cerebral cortex, the cholinergic neurons of the basal forebrain are modulated in turn by neurotransmitters which may include acetylcholine released from processes of brainstem or forebrain neurons. In the present study, we examined the effect of carbachol, a non-specific cholinergic agonist, either alone or in the presence of N-methyl-D-aspartate upon electrophysiologically identified cholinergic basalis neurons in guinea pig basal forebrain slices. Carbachol produced a direct postsynaptic hyperpolarization, accompanied by a decrease in membrane resistance. Muscarine could mimic this hyperpolarizing effect, whereas nicotine produced a direct postsynaptic membrane depolarization. The interaction of carbachol with N-methyl-D-aspartate was subsequently tested since, in a prior study, N-methyl-D-aspartate was shown to induce rhythmic bursting in cholinergic cells when they were hyperpolarized by continuous injection of outward current. Applied simultaneously with N-methyl-D- aspartate in the absence of current injection, carbachol was also found to promote rhythmic bursting in half of the cells tested. Since the bursts under these conditions were markedly longer in duration than those observed in the presence of N-methyl-D-aspartate alone, it was hypothesized that carbachol might have another action, in addition to the membrane hyperpolarization. Using dissociated cells, it was found that brief applications of carbachol could indeed diminish the slow after hyperpolarizations that follow single spikes, short bursts or long trains of action potentials in cholinergic basalis neurons. These results indicate that, through its dual ability to hyperpolarize cholinergic neurons and to reduce their after hyperpolarizations, acetylcholine can promote the occurrence of rhythmic bursting in the presence of N-methyl-D-aspartate. Accordingly, whether derived from brainstem or local sources, acetylcholine may facilitate rhythmic discharge in cholinergic basalis neurons which could in turn impose a rhythmic modulation upon cortical activity during particular states across the sleep waking cycle.

Original languageEnglish
Pages (from-to)47-55
Number of pages9
Issue number1
StatePublished - 26 Aug 1997
Externally publishedYes

Bibliographical note

Funding Information:
We thank Danièlle Machard and Lynda Mainville for their excellent technical assistance. This work was supported by grants from the Swiss Fonds National, the Sandoz and Roche Foundations to MM, as well as by a grant and a fellowship from the Medical Research Council of Canada to BEJ and SW respectively. PF was supported by fellowships from the Fondation Fyssen and La Région Rhône-Alpes.


  • Arousal
  • Basal forebrain
  • Guinea-pig
  • Sleep
  • Slices

ASJC Scopus subject areas

  • General Neuroscience


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