Inhibitory synaptic control of social avoidance behavior

社交回避行为的抑制性突触控制

基本信息

批准号：
8657001
负责人：
Mitra Heshmati
金额：
$ 3.71万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-16 至 2016-04-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8657001
关键词：
American Animal Model Animals Anxiety Disorders Aversive Stimulus Basic Science Behavioral Biological Brain Brain region Cells Chronic Chronic stress Comorbidity Data Depressed mood Development Disease Down-Regulation Electrophysiology (science)Etiology Excitatory Synapse Frequencies Functional disorder Gap Junctions Gene Transfer Infusion procedures Inhibitory Synapse Interneurons Intervention Light Literature Major Depressive Disorder Mediating Mefloquine Membrane Mood Disorders Mus Neurons Nucleus Accumbens Parvalbumins Pathway interactions Patients Play Predisposition Presynaptic Terminals Prevalence Probability Recording of previous events Reporting Resistance Rewards Rodent Role Social Controls Social Interaction Stress Synapses Testing Therapeutic Toxin Transgenic Mice United States Viral Virus avoidance behavior awake behavior test chronic depression driving behavior in vivo novel optogenetics postsynaptic presynaptic research study resilience response reward processing social vesicular GABA transporter

项目摘要

DESCRIPTION (provided by applicant): 1 in 6 Americans report a lifetime prevalence of major depressive disorder; however, one-third of depressed patients are resistant to current treatments. The search for more effective pharmacological interventions relies on a better basic science understanding of the pathophysiology underlying mood disorders. The use of animal models, such as chronic social defeat stress, has furthered our understanding of biological mechanisms underlying susceptibility and resilience to stress. Previous studies in our lab showed an increase in excitatory synapses in the nucleus accumbens (NAc), a brain region critical to the reward pathway, in mice susceptible to social defeat. Preliminary data also shows a decrease in inhibitory presynaptic terminals in the NAc following chronic social defeat stress. We hypothesize that downregulation of inhibitory tone in the NAc underlies susceptibility to stress leading to social avoidance behavior. This proposal seeks to more fully examine chronic social defeat stress- induced changes to inhibitory tone in the NAc GABAergic microcircuit and to investigate the contribution of fast- spiking, parvalbumin interneurons to social avoidance behavior.

描述（由申请人提供）：六分之一的美国人报告了重度抑郁症的终生患病率；但是，三分之一的抑郁症患者对当前治疗有抵抗力。寻求更有效的药理学干预措施依赖于对病理生理的更好的基础科学理解。动物模型的使用，例如慢性社会失败压力，进一步扩大了我们对压力敏感性和韧性的生物学机制的理解。我们实验室中先前的研究表明，在容易受到社会失败的小鼠中，伏隔核（NAC）的兴奋性突触增加。初步数据还显示了慢性社会失败压力后NAC中抑制性突触前终端的减少。我们假设NAC中抑制性语调的下调是压力导致社会回避行为的敏感性的基础。该提案旨在更充分地检查NAC GABA能微电路中慢性社会失败压力引起的抑制性抑制作用的变化，并研究快速尖峰，白蛋白酶中间神经元对社会回避行为的贡献。