The results of recent studies indicate that selective lesions of the cholinergic neurons projecting from the substantia innominata (SI)/nucleus basalis (nBM) to cortical regions produce deficits in increasing, but not decreasing attention to a conditioned stimulus in rats. As a complementary approach to these lesion studies, neurobiological methods will be used in the proposed research to examine in greater detail the cortical systems involved in attentional processing. Expression of c-fos , as a possible neuronal indicator of cholinergic activation, will be used to anatomically map the cortical systems involved in incrementing attention to a cue (Specific Aim 1). Once a behaviorally-induced c-fos response is established, the effect of removal of SI/nBM cholinergic neurons on both behavioral performance and c-fos induction will be examined, to determine if the observed cortical activation depends on basal forebrain cholinergic input (Specific Aim 2). The results of neuropsychological studies have shown that certain regions of cortex, such as parietal cortex, are involved in the regulation of attentional processes. Our preliminary findings indicate that discrete cortical regions (e.g., within parietal cortex) are activated at different timepoints when attention is increased. The cholinergic projections to specific cortical regions will be removed to examine the role of discrete corticopetal subunits and cortical regions in increasing attention (Specific Aim 3). These studies may provide an important and useful animal model that bears on our understanding of mechanisms of attention in humans. Such a model may be of particular use in identifying the basis of attentional deficits associated with aging, Alzheimer's Disease, and schizophrenia.
