This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this project has been to use electron microscopic techniques to determine the localization of the D1 and D5 dopamine receptors and their signaling proteins within primate prefrontal cortex, and identify any physical interactions between these receptors and their downstream effector proteins utilizing immunoprecipitation methods. The prefrontal cortex has a complicated circuitry, and understanding where these two receptors are located within specific elements of this circuitry will deepen our understanding of how D1 family receptor signaling effects prefrontal functioning. We have previously determined the localization of D1 and D5 in prefrontal cortex (PFC) neuropil of layers I, III and V;determined their co-localization within dendritic spines and axon terminals of layer III;and determined D1 and D5 localization to parvalbumin and calretinin interneuron dendrites and axon terminals. During the reporting period, we determined the neuropil localization of two D1 and D5 signaling proteins, DARPP-32 and Inhibitor-1, in layer III of the primate PFC;determined their localization within dendritic spines and axon terminals;and determined their localization to parvalbumin and calretinin interneurons. We also determined the localization of two protein phosphatase-1 (PP1) isoforms to parvalbumin and calretinin interneurons, and have compared the neuropil and interneuron localization of all proteins of interest (D1, D5, DARPP-32, I-1, and PP1 isoforms) to derive individual signal transduction environments for each type of neuronal compartment.
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