The effect of atropine administered in the medial septum or hippocampus on high- and low-frequency theta rhythms in the hippocampus of urethane anesthetized rats

Cholinergic mechanisms are critical for the generation of hippocampal theta rhythm. Cholinergic innervation of the hippocampus originates from the medial septum (MS) and cholinergic receptors are expressed in both the MS and hippocampus. In this study, we compared the effects of the muscarinic receptor antagonist atropine in the MS and the hippocampus on theta generation. Hippocampal theta rhythm was elicited by electrical stimulation of the pontine reticular formation using series of stimuli with varying intensities. Atropine was administered either systemically (50 mg/kg i.p.) or locally in the MS (microdialysis; 25 and 75 mM for 30 or 90 min) or in the hippocampus on one side (microinjection; 20 or 40 ug). The relative power at the peak theta frequency was calculated and averaged over episodes of low-intensity and high-intensity stimulations. We found that atropine drastically reduced theta rhythmic synchronization when injected in either location. After MS administration of atropine, however, high-frequency theta elicited by high-intensity stimuli was more resistant (58% and 67% decrease after 25 mM and 75 mM atropine, respectively) than slow theta elicited by low-intensity stimuli (86% and 91% decrease). There was no significant difference between the powers of the two oscillations after hippocampal injections (70-75% decrease). We conclude that the theta suppressing effect of atropine involves both hippocampal and septal mechanisms and that low-frequency theta as compared with fast theta rhythm is more sensitive to muscarinic acetylcholine receptor antagonism in the MS but not in the hippocampus.