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Cholinergic neurons in the basal forebrain participate in consciousness and general anesthesia

Leung LS, Petropoulos S, Ma J, Shen B (2004) Cholinergic neurons in the basal forebrain participate in consciousness and general anesthesia. Neuroscience 2004 Abstracts 565.4. Society for Neuroscience, San Diego, CA.

Summary: Acetylcholine (Ach) in the brain has long been associated with consciousness. In this study, we assessed consciousness in rats by their EEG and behavioral responses to a general anesthetic. Cholinergic neurons in the nucleus basalis of Meynert (NbM) were lesioned by bilateral injection of toxin IgG192-saporin (0.15 μg at P1.4, L2.7, 7.7 mm below dura) in 10 adult male rats. Control (5 rats) had saline injected into the NbM. EEGs were recorded by electrodes placed in layer V of the frontal cortex (FC) and visual cortex (VC). Spectral analysis of the spontaneous EEGs in FC and VC during awake-immobility indicated that lesioned animals showed higher delta (0.8 to 4 Hz) and lower gamma (30- 58 Hz) power as compared to controls. Subsequent acetylcholinesterase staining (optical density) confirmed significant Ach depletion in both FC and VC, in the lesion as compared to the control group (P<0.002, Wilcoxon). When challenged with a normally subanesthetic dose of general anesthetic, the lesioned rats showed, as compared to controls, significantly longer durations of loss of righting and tail-pinch response after 5 mg/kg i.v. propofol (P<0.001), but not after 20 mg/kg i.p. pentobarbital or 2% halothane. In correspondence with the deep behavioral anesthesia, delta power at FC after propofol was significantly larger in lesioned than control rats. Lesioned rats, as compared to controls, also showed decreased locomotion (behavioral excitation) when given 2% halothane in a large chamber. In summary, a loss of Ach in the neocortex decreases the level of consciousness as indicated by increased delta and decreased gamma EEG, and by an increased sedative/ anesthetic response to propofol i.v. We suggest that patients with Alzheimer disease may show altered response to some general anesthetics.

Related Products: 192-IgG-SAP (Cat. #IT-01)

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