The actions of cholinomimetics and of physostigmine were tested on two parameters reflecting hippocampal activity, namely θ activity and pyramidal cell excitability. In rats pretreated with methylscopolamine and anaesthetized with urethane i.v. administration of the cholinomimetics oxotremorine and arecoline and the cholinesterase blocker physostigmine evoked θ wave activity in the hippocampus, which was blocked by scopolamine. Spectral analysis demonstrated that the frequency of the θ waves induced was dose-related, ranging from about 3 Hz to between 5 and 6 Hz. θ Activity could not be induced by arecoline in animals with large septal lesions. Pyramidal cell excitability is known to be increased by endogenous acetylcholine released from cholinergic fibres. In the present study, however, i.v. injections of oxotremorine, arecoline and physostigmine in doses that induce θ activity diminished the excitability of CA1 pyramidal cells in a dose-dependent manner, as judged by the reduction in the amplitude of the population spike and the dendritic epsp. These depressant effects were attenuated by scopolamine but not by methylscopolamine. The depressant effect of arecoline was attenuated in rats with extensive lesions in the medial septal area. The present findings demonstrate that exogenously administered cholinomimetics only partly mimic the action of endogenous acetylcholine in the hippocampus. The central sites of action of exogenously administered cholinomimetics for mediation of θ activity and alteration of pyramidal cell excitability remain to be elucidated.
- Cholinesterase blockers
- Pyramidal cells
- θ Rhythm
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience