The proposed research will examine the interstitial nuclei of the human anterior hypothalamus (INAH) for volumetric variation associated with infection with the human immunodeficiency virus in an experimental design that assesses and controls for variation associated with age, gender category, and various sequelae of infection. The cellular parameters (i.e., cell size and number) that give rise to any such confirmed volumetric variation will be determined. A detailed analysis of the cellular phenotypes that comprise the INAH will be done using immunocytochemistry and in situ hybridization to localize a variety of peptides, enzymes and putative neurotransmitters. The significance of the proposed research is that it will provide the first detailed analysis of the cellular phenotypes of the human INAH. The proposed research may: resolve discrepancies among laboratories regarding hormonal influences on brain structure developmentally and in adulthood, suggest ways in which HIV influences brain structure, facilitate functional studies by suggesting homologies between specific human INAH and specific hypothalamic nuclei of laboratory animals. In addition to raising interesting questions about the mechanisms linking the structure of the brain to its function, hypothalamic variations in animals have provided powerful models for studying the cellular and molecular aspects of neural development and its hormonal regulation. Confirmation of similar variations in the human hypothalamus could similarly provide insights into important neurodevelopmental mechanisms of potentially broad clinical significance.
