The longer-term objective of this project is to study the synaptic interaction of two major components of the forebrain: the limbic cortex and the striatum. The specific aims are to establish in detail the physiological and pharmacological properties of projections from limbic cortex to the striatum at a cellular level. Research will focus on one particular pathway -- projections from the entorhinal cortex to the NAc. Research will be performed in the in vivo rat preparation using intracellular recording, intracellular labeling of single cells with horseradish peroxidase (HRP), and multibarrel iontophoresis. The combined application of these advanced procedures will be used to establish details about neuronal interactions. Hence, the present studies are designed to obtain physiological, morphological, and neuropharmacological data regarding the synaptic relationship of these areas, including information about their circuit properties and transmitter substances. The NAc is an important component of the ventral striatum. The entorhinal cortex is a key structure of the hippocampal formation, and much hippocampal input and output is funnelled through it. Direct projections from the entorhinal cortex to the NAc have been demonstrated by modern neuroanatomical tracing techniques. However, despite this close, one-way neuroanatomical relationship, the applicant claims that no publishable cellular physiological or pharmacological data have been forthcoming in this research area to date. The present project plans to focus on the following questions concerning: (1) the synaptic organization of projections from the entorhinal cortex to physiologically and morphologically defined NAc neurons; (2) which glutamatergic receptor subtypes mediate excitatory responses of NAc neurons to synaptic inputs from the entorhinal cortex; (3) which gamma aminobutyric acid (GABA)ergic receptor subtypes mediate the secondary inhibitor of striatal neurons to synaptic inputs from the entorhinal cortex; and (4) how excitatory inputs to the NAc from distinct regions of limbic cortex interact at the level of single NAc neurons. The NAc has been implicated in drug abuse and mental illness, including mania and schizophrenia. There is also some suggestive evidence that the entorhinal cortex may be involved in schizophrenia by virtue of histopathological abnormalities observed in the brains of schizophrenic patients. Accordingly, the broader significance of the current project may be its possible relevance to understanding interactions between the limbic cortex and striatum in the production of psychotic symptoms and drug treatment side-effects.