CORTICAL CIRCUITRY RELATED TO NEUROTRANMISSION PROTEINS

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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. This work relates prefrontal cortical circuitry with the molecular components of dopamine neurotransmission. The results relate to the circuitry of working memory, which is dysfunctional in schizophrenia. Working memory function depends on an optimal level of D1 receptor activation and is impaired by both over and under stimulation of D1 receptor. It is hoped that our results will lead to a better understanding of the mechanism of the D1 receptor's complex modulation of working memory, and ultimately to a better understanding of antipsychotic drug action. We have used post-embedding immunogold labeling to examine the distribution of PP1 targeting proteins (spinophilin and neurabin) and PP1(alpha) and PP1(gamma1) in spines. Our data indicates that the D1 receptor has access to different complements of signal transduction proteins in different neuronal compartments and suggests functional differences for the two PP1 isoforms. The finding that not all dendritic spines are equal, but that different populations of spines have different sets of signal transduction proteins provides new mechanisms for varying the effect of different inputs onto single neurons. Finally we have used single and pre-embedding double label methods to examine the subcellular localization of group I mGluRs (mGluR1a and mGluR5) and determined a number of differences in their distribution, both between each other, between monkey cortex and rat cortex and between cortex and basal ganglia.