D1 and D5 Receptor Signaling in Monkey PFC

描述(由申请人提供)：多巴胺受体(D1R)家族的多巴胺能神经传递对正常认知功能至关重要，该系统的损害与精神分裂症症状和可卡因滥用有关。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，D1R药物在PFC中存在特殊而复杂的回路效应，这表明多巴胺在D1和D5受体上的作用是一个结构成分。因此，这项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来研究作用于D1和D5受体的多巴胺如何调节PFC的活动。第一个目标将确定D1和D5受体在PFC电路的特定组件中的定位。由于D1R激活的效果依赖于一个复杂的信号转导途径，第二个目的将决定该途径中的关键蛋白是否可用于PFC电路中特定组件中的每个D1R。第三个目标将通过识别D1R下游靶点，如NMDA、AMPA和GABA受体，与D1和D5以及两个关键的D1R信号转导蛋白特异地相互作用，来扩大神经解剖学的发现。

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.