Early damage to large portions of the medial temporal lobe has far more severe consequences on the development of cognitive and socioemotional behavior in primates than late damage. The new program of studies described in the proposal is aimed at following these earlier findings in defining which structures in the medial temporal lobe are crucial for the development of normal memory abilities and the formation and establishment of social bonds. We will begin with a study of the effects of early vs. late damage to the hippocampal formation. Earlier studies have often suffered either from the lack of discrete lesions, comprehensive histological analysis or appropriate and sophisticated behavioral assessment, such that the lesion effects reported are inconclusive. The program of studies outlined in this application uses sophisticated MRI-guided excitotoxic hippocampal lesions newly designed memory tasks, extensive characterization of behavioral changes and state of the art anatomical techniques to investigate a) the development of hippocampal functions in monkeys, b) the long-term consequences of early vs. late hippocampal insult on the maturation of memory processes and social bonds, c) the anatomical organization of the efferent projections systems from entorhinal, perirhinal, and parahippocampal areas and, d) the anatomical reorganization of these efferent systems as a result of early hippocampal lesions as compared to adult lesions. Considering that dysfunction of the hippocampal formation contributes to behavioral changes accompanying several devastating neurological disorders, including Dementia, Alzheimer's disease, Schizophrenia and Autism, this unique program of research in monkeys will ultimately lead to the discovery of ways in which such disorders can be alleviated or even eliminated.
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