Cholinergic nucleus basalis neurons are excited by histamine in vitro

A. Khateb, P. Fort, A. Pegna, B. E. Jones, M. Mühlethaler

Research output: Contribution to journalArticlepeer-review


Considerable evidence has shown that both cholinergic and histaminergic neurons in the brain may act to facilitate processes of cortical activation that occur during wakefulness. In the present study, the potential influence of histaminergic neurons upon cholinergic neurons of the basal forebrain was investigated in guinea-pig basal forebrain slices. We found that electrophysiologically identified and immunohistochemically verified cholinergic neurons of the nucleus basalis were depolarized and excited by histamine, as manifested by an increase in tonic firing. The depolarization was associated with an increase in membrane input resistance. The effect of histamine persisted in the presence of either tetrodotoxin or a high-magnesium/low-calcium solution, indicating that it is postsynaptic. By a process of elimination, the participation in this response of the three described histamine receptors was examined. Involvement of H3 receptors was excluded on the basis that the H3 agonist (R)-α-methyl-histamine had no direct effect, and the H3 antagonist, thioperamide, did not block the effect of histamine. In contrast, the presence of a small response to impromidine, a selective agonist of H2 receptors, and the partial block of the response to histamine by the H2 receptor antagonist, cimetidine, indicated the participation of H2 receptors. Finally, the complete elomination of histamine's effect occurred when low doses of the H1 antagonist, mepyramine, were added to the H2 antagonist, cimetidine, indicating the involvement and predominance of H1 receptors in the response. Our data thus suggest that histamine excites nucleus basalis cholinergic neurones by a concomitant activation of H1 and H2 receptors. Histaminergic tuberomammilary neurons may accordingly facilitate tonic firing of cholinergic neurons during wakefulness. Cholinergic basalis neurons could thus act in tandem with histaminergic neurons during periods of arousal to collectively promote widespread cortical activation.

Original languageEnglish
Pages (from-to)495-506
Number of pages12
Issue number2
StatePublished - Nov 1995
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements--We thank Dani61e 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 M.M., as well as by a grant from the Medical Research Council of Canada to B.E.J.P.F. was supported by grants from the Fondation Fyssen and La R6gion Rh6ne-Alpes.


  • ChAT
  • TTX
  • arousal
  • basal forebrain
  • choline acetyltransferase
  • guinea-pig
  • sleep
  • tetrodotoxin

ASJC Scopus subject areas

  • General Neuroscience


Dive into the research topics of 'Cholinergic nucleus basalis neurons are excited by histamine in vitro'. Together they form a unique fingerprint.

Cite this