The purpose of this NIMH Physician Scientist Award is to gain skills as an independent researcher to explore the neuroanatomic basis of schizophrenia. the role of the basal ganglia in mediating integration of diverse inputs form motor-, association-, and limbic-related cortices and how faulty integration within the basal ganglia may be manifest in the complex symptomatology of schizophrenic patients will be studied. The ventral striatum and globus pallidus, may represent portions of the basal ganglia where integration of motor- and limbic-related pathways occurs by virtue of their connections to both functional regions. The Phase I portion (years 1-2) of the fellowship program involves general graduate coursework in neuroanatomy, neurophysiology, and neuroendocrinology and seminars concerning general topics in neuroscience and basal ganglia function. Introductory research experience will be obtained by working with Dr. Haber on ongoing and independent laboratory experiments which center on examining the integration of limbic and motor- related pathways of the basal ganglia. The Phase II portion (years 3-5), of the training program involves independent experiments, initially in rodents, designed to explore the role of the efferent projections of the ventral pallidum as potential mediators of limbic and motor integration and the mechanisms by which this integration occurs. These experiments will explore the differential projections of dorsal (motor) and ventral (limbic) pallidum to the substantia nigra, subthalamus nucleus and ventral tegmental area; whether collateralization of ventral pallidal efferent fibers to cells in the ventral pallidum which project to limbic and non-limbic regions. Anterograde tracers (PHAL, titrated amino acids, WGAS-HRP) and retrograde tracers (fluorescent dyes, WGA-HRP) in combination with peptide and tyrosine hydroxylase immunocytochemistry will be utilized in these experiments.
