The hippocampal formation and prefrontal cortex (PFC) have both been demonstrated to participate in working memory processes, and the hippocampo-prefrontal pathway has been suggested to play an important developmental role in the pathology of schizophrenia. Dopamine (DA) afferents from the ventral tegmental area (VTA) have also been implicated in the learning and memory functions of the hippocampus and the PFC, and dysfunction of ascending DA projections has been suggested to be involved in the neuropathology of schizophrenia. It is not known, however, whether DA afferents are able to modulate hippocampo-prefrontal transmission. The proposed research will utilize in vivo neurophysiological methods in rats to examine the ability of DA, applied locally or released by VTA stimulation. to act on this pathway both at the cell body level and in the terminal field. In Study 1, the actions of DA will be recorded on hippocampal neurons identified as projecting to the PFC. In Study 2, the ability of DA to modulate the response of PFC neurons to hippocampal stimulation will be examined. In Study 3, the ability of DA to act presynaptically on hippocampal terminals will be examined by recording the terminal excitability of hippocampal afferents to the PFC. The mechanisms of DA action that are identified in these studies will improve the understanding of its role in cognitive and affective functions, as well as its potential contribution to the pathophysiology and treatment of psychiatric and neurological disorders.
