The neocortical mantle and limbic forebrain structures receive susbtantial cholinergic innervation. Recent experiments have established that virtually all of this innervation arises from cholinergic neurons in the basal forebrain. These cholinergic neurons are found in the septal area, in the diagonal band nuclei and in the nucleus basalis of Meynert. We propose to prepare a detailed atlas of the distribution of these neurons in monkeys and in humans. Furthermore, we will study their transmitter cytochemistry, morphological specializations and connectivity patterns. We will also investigate age-related changes in these cholinergic projection neurons. The relevance of central cholinergic pathways to human disease conditions has recently become the focus of great interest. It has been shown that patients with Alzheimer's Disease have a selective impairment of cortical cholinergic innervation and that this impairment may reflect damage to the nucleus basalis. The cholinergic pathways from the nucleus basalis to the cortical mantle may also be abnormal in schizophrenia, Huntington's Disease and in Parkinsonism. There is reason to believe that some of the age-related changes in cognition are also intimately related to abnormalities in the cholinergic innervation of cortex. Thus, information of central cholinergic pathways may be directly relevant to a wide spectrum of mental and neurological diseases as well as to the cognitive alterations that occur in the course of physiological aging. The methods that we will employ include: immunohistochemistry with monoclonal antibodies to choline acetyltransferase, acetylcholinesterase histochemistry, axonal transport of horseradish peroxidase, tritiated amino acids, and fluorescent tracers, Golgi techniques and 2-deoxyglucose autoradiography.
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