REGIONAL VARIATION IN D1 SIGNALING PROTEIN LOCALIZATION

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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. We study how dopamine acting at D1 family dopamine receptors (D1R; D1 and D5) affects the circuitry of brain regions relevant to schizophrenia, PTSD and substance abuse. These regions include prefrontal cortex (PFC), amygdala and nucleus accumbens (NAc). We completed our examination of D1R in (PFC) and published the results. We have further examined the distribution of D1R in prefrontal interneuron subtypes. We have found distinct patterns of localization of receptors in subpopulations of interneurons and proposed a detailed model for how dopamine stimulation of D1 family receptors controls pyramidal cell. A manuscript of this work is in press. We completed our study of D1R in monkey and rat amygdala, a brain region implicated in fear and anxiety disorders, as well as drug addiction. We found differences in the distribution between D1 and D5 and between PFC and amygdala. We found similar patterns of distribution between rat and monkey amygdala and similar cellular responses in monkey compared to previous reports in rat. These results are being prepared for submission. In addition, we examined the interneuron subtypes of the primate amygdala and found that PV interneurons in monkey are similar to those seen in rat. This work is in press. Our studies of D1R in NAc are nearly complete, and we are characterizing the distribution of components of the D1R signal transduction pathway: DARPP-32 and inhibitor-1. We have completed our analysis in PFC and are preparing a manuscript for submission. We are working to complete our analysis in the amygdala and NAc. Our study of the protein Lfc has pioneered a new localization assay and has been published. Finally, we published a study of mGluR2/3 in different parts of the amygdala and confirmed that our analyses reveal functionally significant differences.