DOPAMINE INTERACTIONS WITH HIPPOCAMPAL MOSSY CELLS

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Project Description. Mossy cells are pivotal cells governing information flow through the hippocampal formation, and they represent the first excitatory inputs to newly born granule neurons in the adult. Mossy cells therefore have an important role in governing hippocampal function in neuropsychiatric health and dysfunction. Although dopamine modulates synaptic function and plasticity in the hippocampus, the specific cellular targets and the nature of dopamine interactions are unclear. Circumstantial evidence suggests that mossy cells are privileged recipients of dopamine input to the hilus region of the hippocampal formation. This evidence drives our hypothesis, to be functionally tested, that mossy cells are the sole recipients of endogenous dopamine actions in the hilus To help explain mossy cells as privileged recipients, we hypothesize that dopamine acts through conventional synaptic contacts rather than volumetrically. We will use optogenetic stimulation techniques to probe dopamine and other catecholamine inputs to mossy cells and other cells of the hilus to characterize the nature of physiological dopamine responses. In a second level of interrogation, we will use channel-based biosensors expressed in cells of the hilus to test the hypothesis that dopamine exposure of mossy cells is through conventional synaptic contacts rather than through volumetric signaling. Our studies elucidate the puzzling sparse DA innervation of the hilus by hypothesizing cell-specific actions of DA at a cell type that gates information flow through the hippocampus. Successful completion of these studies will provide tools and preliminary data for a more expansive examination of DA effects on hippocampal circuitry and role of specific cellular interactions in behaviors relevant to neuropsychiatric health and dysfunction.