The dopaminergic projection to the nucleus accumbens is the target of clinically effective antipsychotics and it has been implicated in the pathophysiology of schizophrenia. In addition, several imaging studies have shown a number of cortical regions to be also affected in this disorder, including the prefrontal cortex and hippocampal formation. Establishing how these systems interact with each other will provide a significant advance in our understanding of the neural basis of this devastating disorder. The nucleus accumbens is a brain region that could integrate these seemingly unrelated neural systems within a single conceptual framework. Indeed, this brain region has connections with virtually every area implicated in this disease. Unveiling the mechanisms of information integration in the nucleus accumbens is a major goal in our research efforts. In this proposal, we plan to assess the role of dopamine, hippocampal and other limbic inputs in the control of nucleus accumbens cell activity. We will study the impact of these inputs on the transitions between the active and silent states accumbens neurons exhibit. The hippocampal gating of cortical throughput in the nucleus accumbens previously proposed by us, as well as the involvement of other limbic inputs in the control of prefrontal-accumbens responses will be assessed with simultaneous recordings of electrical activity in the hippocampus and the nucleus accumbens. The actions of monoamines (also implicated in schizophrenia) on nucleus accumbens cell excitability and activity states will be studied using both in vivo and in vitro intracellular recordings. Finally, the potential role of gap junction-dependent transfer of information between accumbens neurons on the synchronization of active states will be assessed by performing dual whole-cell clamp recordings in vitro from pairs of coupled cells.
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