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

项目摘要 社会性包括一系列复杂的行为，需要多个神经回路的协调活动 成功的表达。有效的社会参与是高度有益的，并依赖于μ阿片受体 这是大脑中一个重要的奖励中心--丘脑核内的信号。选择性阻断mu 延髓核内的阿片受体抑制社会互动，而刺激这些受体， 受体显著增加了社会互动。由于μ阿片受体在突触前轴突上表达， 终末以及各种突触后细胞在突触核，机制，其中亩 阿片受体控制社会反应仍不清楚。因此，本建议的总体目标是 了解神经核微电路上的μ阿片受体如何介导社会行为。重点 这一建议的重点将是中棘投射神经元，它构成了大脑皮层的主要细胞类型。 丘脑核中型棘状神经元通过其Drd1或Drd2多巴胺的表达来区分 受体亚型，并且这些不同细胞类型的激活对奖赏相关行为具有不同的影响。 输出.在这个建议中，我将选择性地操纵μ阿片受体在中等多刺 神经元亚型，并表征所得的细胞和社会表型（目的1）。此外，我将使用 在μ阿片样物质后恢复特定中型多棘神经元亚型抑制性调节的化学遗传学 受体缺失，并确定对社会行为的影响（目的2）。该项目将阐明μ阿片类药物 受体活性以一种 是社会行为表达的必要条件。通过我的培训，我将获得背景，概念和 技术知识，以完成这一建议。我的保证人帕特里克罗斯韦尔博士和共同保证人凯文博士 威克曼，提供出色的指导，专注于我的技术和专业发展， 神经学家此外，明尼苏达大学神经科学研究生课程提供了一个支持 和合作的科学环境，并有许多核心设施，将提供给我的培训 和设备使用。拟议的项目将帮助我成为一个独立的研究科学家，因为我发展 识别和询问神经精神疾病中出现的细胞、电路和行为异常的能力 疾病

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.