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The Journal of Neuroscience, 2002, 22:RC200:1-6

RAPID COMMUNICATION
The Septohippocampal System Participates in General Anesthesia

Jingyi Ma^{1, 2}, Bixia Shen^{1, 2}, Lee S. Stewart^{1, 4}, Ian A. Herrick³, and L. Stan Leung^{1, 2, 4}

Departments of ¹ Physiology, ² Clinical Neurological Sciences, and ³ Anaesthesiology, and ⁴ Program in Neuroscience, University of Western Ontario, London, Ontario, Canada N6A 5A5

How the brain mediates general anesthesia is not known. We report that two interconnected structures in the forebrain, the medial septum and the hippocampus, participate in maintaining awareness and movements during general anesthesia. In the awake, freely behaving rat, inactivation of the medial septum or the hippocampus by local injection of a GABA_A receptor agonist, muscimol, decreased the dose of a general anesthetic needed to induce a loss of the tail-pinch response or a loss of righting reflex. Septohippocampal inactivation also suppressed the behavioral hyperactivity or the delirium stage associated with general anesthesia. An increase and decrease of 30-50 Hz (gamma) waves in the hippocampus correlated with an increase and decrease in behavioral activity, respectively. Similar results were found for both volatile (halothane and isoflurane) and nonvolatile (propofol and pentobarbital) anesthetics. We conclude that the behavioral hyperactivity induced by a general anesthetic is mediated in part by the septohippocampal system, and that depression of the septohippocampal system increases the potency of a general anesthetic. It is suggested that more potent general anesthetics or adjuvants may be developed by maximizing the pharmacological depression of the septohippocampal system.

Key words: delirium; general anesthetic; gamma rhythm; medial septum; hippocampus; propofol; pentobarbital

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Copyright © Society for Neuroscience  0270-6474//$05.00/0

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