candidate's abstract): This is a competitive renewal of an RSDA that proposes to use in vivo and in vitro electrophysiological recordings to examine the functional interactions among cortical afferents and the DA system within the NAC of rats. Studies into the etiology of schizophrenia have recently focused on a cortical locus of pathology with emphasis on the prefrontal cortex and the hippocampus. Moreover, owing to the genetic linkage schizophrenia, the impact of developmental disruption has gained prominence in this field. As an extension of our studies demonstrating a gating role for hippocampal input into the NAC, we propose to evaluate the functional interaction NAC afferents and how it may selectively altered by neonatal disruption according to the following specific aims: (1) To characterize the physiology and pharmacology of the responses evoked in NAC neurons in vitro by stimulation of prefrontal cortical, hippocampal, and amygdalar afferents. (2) To examine the pharmacology of DA actions on each of these afferent systems in vitro. (3) to characterize the response properties and types of interaction between pairs of afferents to NAC neurons recorded in vivo. (4) To examine how the DA system affects the afferent-evoked responses and their interactions in vivo, and how these interactions may be altered by psychotropic drugs. This comprehensive characterization of afferent interactions will provide the necessary baseline data for the last specific aim: 5) To compare the effects of developmental disruption in neonates on the interaction between excitatory afferents to the NAC neurons and their regulation by DA in adults. In this way we will gain a better understanding of the nature of these cortical interactions within the NAC, how these systems are modulated by DA, and how they may undergo a compensatory reorganization as a consequence of neonatal damage. In addition to the research plan, an outline for scientific growth over the next five years is presented. This consists of: (1)expanding my participation in basic and clinical research and training; (2) increasing involvement in scientific organizations; (3) taking a leadership role in organizing program project-based research; and (4) expanding the breadth and depth of my laboratory research. This latter goal will be achieved through combination of collaborative ventures using ultrastructural and viral tract tracing techniques, as well as implementing new technologies into my laboratory, including developmental studies and visual patch recordings. Each technique is advanced to address specific research questions rather than simply expanding my technical base.
