CHOLINERGIC NUCLEUS BASALIS NEURONS ARE EXCITED BY HISTAMINE IN-VITRO

Considerable evidence has shown that both cholinergic and histaminergi c neurons in the brain may act to facilitate processes of cortical act ivation that occur during wakefulness. In the present study, the poten tial influence of histaminergic neurons upon cholinergic neurons of th e basal forebrain was investigated in guinea-pig basal forebrain slice s. We found that electrophysiologically identified and immunohistochem ically verified cholinergic neurons of the nucleus basalis were depola rized 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 o f either tetrodotoxin or a high-magnesium/low-calcium solution, indica ting that it is postsynaptic. By a process of elimination, the partici pation in this response of the three described histamine receptors was examined. Involvement of H-3 receptors was excluded on the basis that the H-3 agonist (R)-alpha-methyl-histamine had no direct effect, and the H-3 antagonist, thioperamide, did not block the effect of histamin e. In contrast, the presence of a small response to impromidine, a sel ective agonist of H-2 receptors, and the partial block of the response to histamine by the H-2 receptor antagonist, cimetidine, indicated th e participation of H-2 receptors. Finally, the complete elimination of histamine's effect occurred when low doses of the H-1 antagonist, mep yramine, were added to the H-2 antagonist, cimetidine, indicating the involvement and predominance of H-1 receptors in the response. Our dat a thus suggest that histamine excites nucleus basalis cholinergic neur ons by a concomitant activation of H-1 and H-2 receptors. Histaminergi c tuberomammillary neurons may accordingly facilitate tonic firing of cholinergic neurons during wakefulness. Cholinergic basalis neurons co uld thus act in tandem with histaminergic neurons during periods of ar ousal to collectively promote widespread cortical activation.