The broad aim of this study is to determine whether basal forebrain cholinergic neurons (BFCNs) can induce anterograde trophic effects on subsets of presumed cortical neurons (labeled with the nonphosphorylated neurofilament marker, SMI-32) with which they contact. Thus, the specific aims are to test the following hypothesis: 1 Morphologically enhanced SMI-32(+) neurons, found in basal forebrain-cortical co-cultures, are of cortical origin and require contact specifically with BFCNs for their enhancement. 2 SMI-32(+) neurons, that have been morphologically enhanced by co-culturing with BFCNs, display enhanced viability in situations that normally result in cell loss. Life span and resistance to kainate induced injury will be examined to determine viability. Possible changes in calcium management will be examined as they may reflect differences in vulnerability to kainate induced injury. Characterizing the regulation of morphological features and survival of certain neocortical cells by BFCNs will be important for understanding the function of cholinergic projections from the basal forebrain to cortex and for understanding cognitive and attentional deficits commonly associated with Alzheimer's disease.
