DIFFERENTIAL ALTERATIONS OF CORTICAL CHOLINERGIC AND NEUROTENSIN MARKERS FOLLOWING IBOTENIC ACID LESIONS OF THE NUCLEUS BASALIS MAGNOCELLULARIS

The present study determined whether cortical cholinergic neurons recover functionally following the loss of afferent projections from the nucleus basalis magnocellularis (nbm). At various time points following ibotenic acid lesions of the nbm, choline acetyltransferase (ChAT) activity or the capacity of cortical cholinergic neurons to synthesize [H-3]acetylcholine (ACh) from the precursor molecule [H-3]choline were measured in the frontoparietal cortex. First, cortical ChAT activity was decreased by 21% and 35% on the side ipsilateral to the lesion at 1 and 2 weeks following the nbm lesion, respectively. By 6 weeks following nbm lesions, cortical ChAT activity returned to control levels and remained at control levels at 10 weeks following nbm lesions. However, by 13 weeks following nbm lesions, we observed a 21% increase in ChAT activity on the side ipsilateral to the lesion. ChAT activity in the nbm remained unchanged over the time course studied. Secondly, there was a parallel reduction (by 43%) in the capacity of frontoparietal cortex slices from the side ipsilateral to the lesion to synthesize [H-3]ACh by 2 weeks following nbm lesions. By 13 weeks following the lesion there was a significant increase (29%) in the synthetic capacity of cortical cholinergic neurons compared to the 2 week time point. Third, the content of neurotensin in the frontoparietal cortex was significantly decreased by 25% and 36%, at 2 weeks and 13 weeks following nbm lesions, respectively. Neurotensin levels in the nbm were not affected by ibotenic acid lesions. In contrast, [I-125]neurotensin binding sites in the frontal or parietal cortex were not altered at 2 weeks following nbm lesions. In summary, the results of the present study provide evidence for functional recovery by cortical cholinergic neurons following selective lesions of the nbm. However, the reduction of cortical cholinergic terminals resulting from the lesion appears to cause irreversible trans-synaptic decreases in cortical neurotensin levels.