Elicitation of hippocampal theta by intraseptal carbachol injection in freely moving rats.

Following infusion into the septum of carbachol, a powerful muscarinic agonist, a theta (theta) rhythm was emitted during complete relaxed immobility as well as during automatic movements. This was not seen following administration of the drug within the caudate/putamen, which is rich in muscarinic receptors but which is not believed to be involved in hippocampal theta generation. Local administration of atropine abolished carbachol-induced theta but did not suppress the theta which normally occurs during voluntary movements. These findings clearly demonstrate that at least a component of the hippocampal theta may be manipulated by intraseptal administration of muscarinic agents, thus supporting our previous assumption that, in theta generation, the septum may be a sensitive site of action for exogenously administered cholinomimetic drugs. They also raise the possibility that the activity of the well identified septohippocampal system involved in the presumed cholinergic hippocampal theta generation is regulated trans-synaptically by acetylcholine at the septal level. Finally, our micropharmacological approach, by suggesting the carbachol-responding septohippocampal cells pacing theta rhythm which is correlated to important functional states, such as attentive waking and active sleep, provides a potential powerful tool for clarifying the neurobiological function of the septohippocampal pathway.