Recent theories regarding the etiology of schizophrenia have shifted their focus from primary pathology in dopaminergic systems to focus on the role of cortical systems and their potential pathological modulation of dopaminergic transmission within the nucleus accumbens. For this reason, this project will examine the interactions within the nucleus accumbens among the excitatory and dopaminergic afferents to this structure. The experiments will characterize the modulation of neocortical excitatory afferents by converging excitatory inputs from the hippocampus and amygdala, and further examine how the influences of these afferents in the accumbens are modulated by dopamine. The effect of dopamine released from the terminals of cells projecting from the ventral tegmental area will be compared with effects of exogenously applied dopamine in order to study the level of localization of dopaminergic modulation. Finally, the effects of dopamine will be further defined in terms of dopamine receptor sub-types with the use of selective antagonists. Studies will first be conducted using in vivo extracellular electrophysiology, in order to provide the applicant with technical skills in electrophysiology and to determine the interactive effects of cortical and limbic excitatory afferents and dopaminergic afferents on action potentials in accumbens neurons. Studies will then move into in vivo intracellular electrophysiology in order to examine these interactions at a synaptic level. The studies will characterize synaptic events that may be altered as a result of pathological changes in the neocortex and temporal lobe associated with schizophrenia.
