D1 and D5 Receptor Signaling in Monkey PFC

猴子 PFC 中的 D1 和 D5 受体信号转导

• 批准号: 7055500
• 负责人: JILL RENEE' Glausier
• 金额: $ 2.81万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7055500
• 关键词: AMPA receptors; GABA receptor; Macaca mulatta; NMDA receptors; biological signal transduction; dopamine; dopamine receptor; immunoelectron microscopy; immunoprecipitation; intermolecular interaction; predoctoral investigator; prefrontal lobe /cortex; protein localization

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.

描述（由申请人提供）：D1多巴胺受体家族（D1 R）的多巴胺能神经传递对于正常的认知功能至关重要，并且该系统的障碍与精神分裂症症状和可卡因滥用有关。但是，D1R信号传导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中存在特定而复杂的电路效应，这表明多巴胺在D1和D5受体中的作用是一种结构成分。因此，该提案的目的是利用免疫组织化学电子显微镜和共免疫沉淀来检查D1和D5受体的多巴胺作用如何调节PFC中的活性。第一个目标将确定D1和D5受体在PFC电路特定组件中的定位。由于D1R激活的效果依赖于复杂的信号转导途径，因此第二个目标将确定在PFC电路的特定组件中，该途径中的密钥蛋白是否可用。第三个目标将通过鉴定下游靶标（例如NMDA，AMPA和GABA受体）来扩展神经解剖学的发现，这些靶标特异性地与D1和D5特别相互作用以及两个关键的D1R D1R信号转导蛋白。