D1 and D5 Receptor Signaling in Monkey PFC

描述（由申请人提供）：多巴胺受体D1家族（D1 R）的多巴胺能神经传递对正常认知功能至关重要，该系统的损伤与精神分裂症神经病学和可卡因滥用有关。然而，D1R信号影响这些功能的确切机制尚不清楚。对单个神经元的研究表明，PFC中存在D1R药物的特异性和复杂的回路效应，表明多巴胺在D1和D5受体上的作用的结构成分。因此，本建议的目标是利用免疫组织化学电子显微镜和免疫共沉淀法来研究多巴胺如何作用于D1和D5受体可以调节PFC中的活性。第一个目的是确定PFC电路的特定组件内的D1和D5受体的本地化。由于D1R激活的影响依赖于复杂的信号转导途径，第二个目标将确定该途径中的关键蛋白质是否可用于PFC电路特定组件中的每个D1R。第三个目标将通过鉴定D1R下游靶点（如NMDA、AMPA和GABA受体）来扩展神经解剖学发现，这些靶点与D1和D5以及两种关键的D1R信号转导蛋白特异性相互作用。

DESCRIPTION (provided by applicant): Dopaminergic neurotransmission at the D1 family of dopamine receptors (D1 R) is critical for normal cognitive functioning, and impairments in this system are linked with schizophrenic symptomology and cocaine abuse. However, the exact mechanism by which D1R signaling affects these functions is not clear. Studies on individual neurons show that there are specific and complex circuit effects of D1R drugs in the PFC, suggesting a structural component for the actions of dopamine at the D1 and D5 receptors. Thus, the goal of this proposal is to utilize immunohistochemical electron microscopy and co-immunoprecipitation to examine how dopamine acting at D1 and D5 receptors can modulate activity in the PFC. The first aim will determine the localization of D1 and D5 receptors within specific components of PFC circuitry. Because the effects of D1R activation rely on a complex signal transduction pathway, the second aim will determine if key proteins in this pathway are available to each D1R in specific components of PFC circuitry. The third aim will extend the neuroanatomical findings by identifying D1R downstream targets such as NMDA, AMPA and GABA receptors that specifically interact with D1 and D5 and two critical D1R signal transduction proteins.