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 (θ) 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 θ generation. Local administration of atropine abolished carbachol-induced θ but did not suppress the θ which normally occurs during voluntary movements. These findings clearly demonstrate that at least a component of the hippocampal θ may be manipulated by intraseptal administration of muscarinic agents, thus supporting our previous assumption that, in θ 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 θ generation is regulated trans-synaptically by acetylcholine at the septal level. Finally, our micropharmacological approach, by suggesting the carbachol-responding septohippocampal cells pacing θ 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.