Behavioral and neurochemical effects following neurotoxic lesions of a major cholinergic input to the cerebral cortex in the rat

The nucleus basalis magnocellularis (NBM) is the name given to a group of cholinesterase-reactive neurons in the ventromedial corner of the globus pallidus of the rat. This cell group appears to be the major extrinsic source of cortical acetylcholine and is believed to be homologous to the nucleus basalis of Meynert in primates. The excitotoxin ibotenic acid (2.4 g/0.4l) was infused bilaterally into the ventromedial globus pallidus. These lesions depleted frontal cortical choline acetyltransferase (CAT) by a third. Neurotoxic lesions of the dorsolateral globus pallidus did not effect cortical CAT activity. Neither lesion affected the rats' performance on a battery of psychomotor tasks or on tests of shock sensitivity. Rats with NBM lesions were mildly impaired in the acquisition of a one-way active avoidance response, but did not differ from the other groups on extinction of the task. The NBM lesioned rats exhibited a severe deficit in the retention of a passive avoidance response. This effect was visible both 24 hours and one hour after training. Experimental controls suggested that the poor performance of the NBM lesioned rats involves a deficit in learning and/or memory of the training trial. Lesions of the dorsolateral globus pallidus also produced an impairment of passive avoidance retention, but this impairment was not as severe as that following NBM lesions. These results are discussed as they relate to the behavioral role of cholinergic innervation of the cortex, and the development of animal models for disorders involving cortical cholinergic deficiencies, including senile dementia of the Alzheimer's type.