Atropine acts in both medial septum and hippocampus to suppress theta rhythm in urethane anesthetized rats

Abstract

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 (AChR) are expressed in both the MS and hippocampus. In this study, we compared the effects of the M1 AChR antagonist atropine in the MS and the hippocampus on theta generation. Hippocampal field potentials were recorded in the CA1 region and at the hippocampal fissure. Theta rhythm was elicited by electrical stimulation (0.2 ms square waves; 100 Hz, 8–10 s) of the pontine reticular formation. The stimulus intensity varied between 0.3 (threshold) and 2.0 mA (maximum effect). Atropine was administered in the MS (microdialysis; 25 and 75 mM for 30 min) or in the hippocampus on one side (microinjection; 20 ug). The relative power at the peak theta frequency was calculated using FFT and averaged over episodes of low-intensity (0.3–0.7 mA) and high-intensity stimulations (0.8–2.0 mA). We found that atropine drastically reduced theta rhythmic synchronization when injected in either location. After MS administration of atropine, high frequency theta elicited by high intensity stimuli was more resistant (58% and 67% decrease after 25mM and 75mM atropine, respectively) than slow theta elicited by low intensity stimuli (86% and 91%). There was no significant difference between the power of the two oscillations after hippocampal injections. 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 M1 AChR antagonism.