Modulation of social behavior by mu opioid receptors in the nucleus accumbens

伏隔核μ阿片受体对社会行为的调节

• 批准号: 10356828
• 负责人: Carlee Toddes
• 金额: $ 1.24万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-02 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10356828
• 关键词: Affect; Animals; Behavior; Behavioral; Brain; Calcium; Cells; Clozapine; Color; Complex; Core Facility; Data; Development; Dopamine D1 Receptor; Dopamine Receptor; Educational Curriculum; Elements; Environment; Equilibrium; Equipment; Excision; Fiber; Imaging Techniques; Impairment; Individual; Infusion procedures; Knowledge; Label; Mediating; Memory; Mentorship; Minnesota; Monitor; Mus; Neurobiology; Neurons; Neurosciences; Nucleus Accumbens; Opioid Antagonist; Opioid agonist; Output; Oxides; Pathologic; Phenotype; Photometry; Population; Presynaptic Terminals; Production; Quality of life; Receptor Inhibition; Receptor Signaling; Reciprocal Social Interaction; Regulation; Research; Research Methodology; Rewards; Rodent; Role; Running; Scientist; Signal Transduction; Social Behavior; Social Controls; Social Interaction; Testing; Therapeutic Intervention; Training; Universities; Viral; Well in self; Wild Type Mouse; base; behavior test; calcium indicator; career; cell type; cellular targeting; common symptom; design; designer receptors exclusively activated by designer drugs; experience; in vivo; insight; motivated behavior; mu opioid receptors; neural circuit; neuropsychiatric disorder; neuropsychiatry; neurotransmitter release; optogenetics; postsynaptic; presynaptic; programs; receptor; receptor expression; relating to nervous system; social; social engagement; targeted treatment; therapeutic target

Project Summary Sociability encompasses a range of complex behaviors that require coordinated activity of multiple neural circuits for successful expression. Effective social engagement is highly rewarding and relies upon mu opioid receptor signaling within the nucleus accumbens, an important reward center of the brain. Selective blockade of the mu opioid receptor within the nucleus accumbens suppresses social interactions whereas the stimulation of these receptors significantly increases social interactions. As mu opioid receptors are expressed on presynaptic axon terminals as well as a variety of postsynaptic cells in the nucleus accumbens, the mechanisms by which mu opioid receptors control social responding remains unclear. Therefore, the broad objective of this proposal is to understand how mu opioid receptors on nucleus accumbens microcircuitry mediate social behavior. The focus of this proposal will be on the medium spiny projection neurons, which constitute the primary cell type of the nucleus accumbens. Medium spiny neurons are distinguished by their expression of Drd1 or Drd2 dopamine receptor subtypes, and activation of these different cell types has distinct effects on reward-related behavioral output. In this proposal I will selectively manipulate the expression of mu opioid receptors on medium spiny neuron sub-types and characterize the resultant cellular and social phenotype (Aim 1). Additionally, I will use chemogenetics to restore inhibitory modulation of specific medium spiny neuron subtype following mu opioid receptor deletion, and determine the impact on social behavior (Aim 2). This project will clarify how mu opioid receptor activity changes medium spiny neuron activity dynamics in the nucleus accumbens in a manner necessary for social behavioral expression. Through my training I will acquire the background, conceptual and technical knowledge to complete this proposal. My sponsor, Dr. Patrick Rothwell, and co-sponsor, Dr. Kevin Wickman, provide outstanding mentorship, focused on my technical and professional development as a neuroscientist. In addition, the University of Minnesota Graduate Program in Neuroscience offers a supportive and collaborative scientific environment and has numerous Core Facilities that will be available to me for training and equipment use. The proposed project will help me become an independent research scientist as I develop the ability to identify and interrogate cellular, circuit and behavioral abnormalities that arise in neuropsychiatric diseases.

项目摘要 社交能力包括一系列复杂的行为，需要多个神经回路的协调活动 才能成功表达。有效的社会参与是非常有益的，它依赖于u阿片受体。 伏隔核是大脑的重要奖赏中心，发出信号。选择性地封锁了这片土地 伏核内的阿片受体抑制社会互动，而刺激这些 受体显著增加了社交互动。阿片受体在突触前轴突上的表达 伏隔核内的终末以及各种突触后细胞，其机制是 阿片受体控制社会反应仍不清楚。因此，这项提议的广泛目标是 了解伏隔核微电路上的u阿片受体如何调节社会行为。焦点 这项建议的重点将放在中棘投射神经元上，这些神经元构成了 伏隔核。中型棘神经元的区别在于它们的DRD1或DRD2多巴胺的表达 受体亚型，这些不同细胞类型的激活对奖赏相关行为有不同的影响 输出。在这项提议中，我将选择性地操纵Mu阿片受体在中棘上的表达。 神经元亚型，并描述由此产生的细胞和社会表型(目标1)。此外，我将使用 化学遗传学恢复Mu阿片类药物后特定中棘神经元亚型的抑制调制 受体缺失，并确定对社会行为的影响(目标2)。这个项目将阐明Mu阿片类药物是如何 受体活性在一定程度上改变伏核中棘神经元的活动动力学 对于社会行为表达来说是必要的。通过我的培训，我将获得背景，概念和 完成此建议书所需的技术知识。我的赞助人，帕特里克·罗斯韦尔博士和共同赞助人，凯文博士 Wickman，提供出色的指导，专注于我作为一名 神经学家。此外，明尼苏达大学神经科学研究生项目提供了一个支持性的 和协作的科学环境，并拥有许多核心设施，可供我进行培训 和设备的使用。建议的项目将帮助我成为一名独立的研究科学家，随着我的发展 识别和询问神经精神病学中出现的细胞、回路和行为异常的能力 疾病。