The research proposed in this application for an ADAMHA Level II Research Scientist Development Award will accomplish several objectives including the acquisition of knowledge! important to mental health research and the continued development of the scientific expertise of the applicant. Dopaminergic (DA) systems have been implicated in the pathophysiology of schizophrenia. 1 Multiple lines of evidence also suggest that the prefrontal cortex is a site of dysfunction or! structural pathology in this disorder. However, relatively little is known about the intrinsic' organization of neural circuits, or about the relation of DA systems to these circuits, in the expanded and highly differentiated prefrontal cortex of primates. The proposed studies will characterize the organization and molecular characteristics of DA neurons that project to, prefrontal cortex, and the interactions of DA afferents with other chemically-identified components of prefrontal cortical circuitry in monkeys. Similar studies will be conducted in human prefrontal cortex in order to determine the extent to which the organization of monkey prefrontal cortex predicts that of the human. These studies will lead to the development and, testing of novel hypotheses regarding the neurobiological bases of schizophrenia. The proposed research will also serve as a vehicle for the continued scientific growth and development of the applicant in several ways. First, these studies involve collaborations with Drs. Jennifer Lund, Anthony Grace and Barry Kaplan at the University of Pittsburgh. These collaborations will enhance the applicant's knowledge and technical expertise in the areas of Golgi impregnations, intracellular staining, and in situ hybridization and related molecular! ; biological methodologies. Second, the applicant will benefit tremendously from interactions with well-established neuroscientists at other institutions. Dr. Floyd Bloom will serve as a general consultant to the proposed studies, providing suggestions and critiques of the applicant's program of research, as well as technical advice on ultrastructural studies. In. addition, discussions and visits to the laboratories of Dr. Patricia Goldman-Rakic will enable the applicant to maximize the scientific yield from the proposed studies of primate neocortex. Finally, the faculty and programmatic activities of the Center for Neuroscience at the University of Pittsburgh offer a wealth of opportunities for the applicant's continuing education. These plans ensure the applicant's continued development as a physician and neuroscientist whose research is focused at the interface of clinical and basic science.
