AGE-RELATED VULNERABILITY OF DEVELOPING CHOLINERGIC BASAL FOREBRAIN NEURONS FOLLOWING EXCITOTOXIC LESIONS OF THE HIPPOCAMPUS

Previous studies have demonstrated that depleting the hippocampus of e ndogenous neurotrophins via excitotoxic lesions fails to alter the via bility of adult cholinergic septal/diagonal band neurons. Since cholin ergic basal forebrain neurons may be more vulnerable during developmen t, we investigated whether excitotoxic lesions produced in neonatal an imals alter the viability of these cells. Postnatal Day 7, 10, 14, and 28 rats pups received unilateral intrahippocampal injections of ibote nic acid and were sacrificed 4 weeks later. At 7, 10, and 14 days of a ge, significant reductions in the number of choline acetyltransferase (ChAT)- and p75 nerve growth factor receptor (NGFr)-immunoreactive neu rons were observed within the medial septum ipsilateral to the hippoca mpal lesion. In contrast, rats receiving similar lesions on Day 28 fai led to display a significant reduction in ChAT-immunoreactive medial s eptal neurons. The magnitude of ChAT-immunoreactive neuronal loss with in the medial septum and the age at which the lesion was made were inv ersely correlated (r(2) = 0.887), indicating that cholinergic septal n eurons become less vulnerable to target removal as the cells develop. Similar results were observed in the vertical limb of the diagonal ban d although a small but significant loss of ChAT-immunoreactive neurons was seen in this structure ipsilateral to the hippocampal lesion when lesions were performed on Postnatal Day 28, At all age groups, many r emaining cholinergic septal/diagonal band neurons appeared dystrophic with stunted fiber outgrowth. The present study demonstrates that unli ke adult rats, removal of hippocampal target neurons during developmen t alters the viability and morphology of cholinergic neurons of the me dial septum and diagonal band. This suggests that target neurons which synthesize endogenous neurotrophins are needed for normal development of cholinergic basal forebrain neurons, but may not be required for t he normal maintenance of the adult cell. (C) 1994 Academic Press, Inc.