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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

基本信息

批准号：
10115524
负责人：
Carlee Toddes
金额：
$ 3.35万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-02 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10115524
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

项目摘要

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.

项目总结