Lesions of the nucleus basalis magnocellularis in immature rats: short- and long-term biochemical and behavioral changes.

Short- and long-term effects of unilateral lesions of the nucleus basalis magnocellularis (NBM) on cortical choline acetyltransferase (ChAT) activity and passive avoidance conditioned responses were examined in immature rats. The lesions were made by stereotaxic injection of quisqualic acid on postnatal days 14 (P14), 17 (P17), and 21 (P21). A marked loss of ChAT activity was found 7 days after surgery in all age groups of lesioned rats. Unoperated P14 rats were unable to perform the passive avoidance conditioned responses. Acquisition began on P17. Lesions made on P17 and P21 strongly impaired the acquisition and retention of the task, evaluated 7 days postoperation. No biochemical but a partial behavioral recovery was observed 3 months after surgery in rats lesioned on P14. On the contrary, despite a persistent decrease in cortical ChAT activity, rats lesioned on P21 were able to acquire and retain the passive avoidance conditioned response. These results indicate that destruction of NBM cholinergic neurons shortly after birth is not compensated for by the developmental plasticity of the residual neurons but results in permanent cholinergic hypofunction. They also demonstrate that cholinergic NBM neurons play an important role in the acquisition and retention of a passive avoidance task; nevertheless, a behavioral recovery may take place 3 months after the lesion, even in the presence of a persistent cholinergic hypofunction.