Profound disturbances of spontaneous and learned behaviors following lesions of the nucleus basalis magnocellularis in the rat.
It has been shown that a marked decline in the cortical activity of the cholinergic synthesizing enzyme choline-acetyltransferase (ChAT), accompanied by a severe neuronal loss in the nucleus basalis magnocellularis of Meynert occurs in the brains of patients with senile dementia of the Alzheimer type. However, the functional role of these neurons is largely unknown. In fact, very few studies have been done in animals. In this paper we report the behavioral effects of the lesion of the nucleus basalis magnocellularis in the rat either by radiofrequency current or by ibotenic acid injection at the level of the cell bodies. The two kinds of lesion lead to a profound disturbance of spontaneous and learned behaviors. There is a complete disorganization of behavior which is evidenced by an enhanced locomotor activity, an alteration in alimentary and hoarding behavior. In addition, we observed a deterioration of spatial memory and an incapacity to reverse a previously learned response. Biochemical assay showed that radiofrequency and ibotenic acid lesions produced a decrease of ChAT activity in the prefrontal and sensorimotor cortices and in amygdala without affecting the hippocampus or striatum. Ibotenic acid lesions seem to specifically destroy the cell bodies of the nucleus basalis magnocellularis since the dopaminergic and noradrenergic fibers of passage remained intact as measured by the unchanged level of endogenous catecholamine concentration in the terminal region in the prefrontal cortex. Presently, it cannot be said that the behavioral syndrome results solely from the lesion of the cholinergic neurons. Also, it is likely that the lesion of the nucleus basalis magnocellularis in the rat does not exactly reproduce the behavioral syndrome observed in Alzheimer's disease in man. However, this experimental approach in leading to a better knowledge of the functioning of these neurones could improve our understanding of this disease.
D000818:Animals; D001479:Basal Ganglia / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D001931:Brain Mapping; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004193:Discrimination Learning / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology; D007858:Learning / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013028:Space Perception / Q000502:physiology; D013377:Substantia Innominata / Q000502:physiology*
D002795:Choline O-Acetyltransferase