Date of Award


Degree Type


Degree Name

Doctor of Philosophy


The purpose of this thesis was to investigate the effects of lesions of the septohippocampal system on hippocampal rhythmical slow activity (RSA) and large amplitude irregular activity (LIA). Slow wave activity was recorded from rat hippocampus during waking behaviors and following the administration of atropine or urethane after either an intraseptal injection of ibotenic acid, an intracerebroventricular injection of ethylcholine aziridinium ion (AF64A) or control solutions. Hippocampal activity was also investigated during quiet and active sleep following ibotenic acid or control treatment.;Ibotenic acid selectively abolished the atropine-sensitive form of RSA normally seen during tonic periods of active sleep and during urethane anesthesia. LIA and RSA in the waking state were somewhat reduced in amplitude but clear RSA persisted during Type 1 behavior (walking, struggling) in the waking state and during phasic muscle twitches in active sleep. In the waking state, the surviving RSA was resistant to atropine, as in normal rats. Analysis of brain sections (Nissl or acetylcholinesterase stains) indicated that ibotenic acid produced cell loss in the dorsal lateral septal and the septohippocampal nuclei. Cells in the medial septal and diagonal band nuclei appeared to be resistant to the ibotenic acid. The results are consistent with the hypothesis that both in the waking and the sleeping state, RSA can be produced by either of two distinctive inputs to the hippocampus. Furthermore, intrinsic septal circuitry appears to be critically involved in the generation of atropoine-sensitive (presumably cholinergic) RSA. No support was found for the idea that RSA during active sleep has a different basis than RSA in the waking state.;AF64A treated rats showed a significantly smaller increase in 6-12 Hz hippocampal activity during struggling than did control rats. However, AF64A did not abolish the presumed cholinergic form of RSA present during urethane anesthesia. Atropine did not alter the RSA seen in waking AF64A treated rats. Analysis of brain sections revealed extensive damage to the fimbria, fornix, corpus callosum, CA3 of the hippocampus, neocortex and striatum. Hippocampal acetylcholinesterase staining appeared normal following AF64A. These data suggest that AF64A is not a selective cholinotoxin since it produces considerable damage to noncholinergic tissue. The apparent selective reduction in hippocampal cholinergic markers suggested by biochemical studies of AF64A may reflect its ability to damage the fimbria and fornix, the major route by which cholinergic septohippocampal neurons reach the hippocampus.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.