Neural Circuits Controlling Resiliency in Dominant Animals

控制优势动物弹性的神经回路

• 批准号: 9023075
• 负责人: Matthew A Cooper
• 金额: $ 45.3万
• 依托单位: UNIVERSITY OF TENNESSEE KNOXVILLE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9023075
• 关键词: Amygdaloid structure; Animals; Anxiety Disorders; Brain region; Cholera Toxin; Clozapine; Complex; Control Animal; Development; Etiology; Exhibits; Exposure to; Extinction (Psychology); FOS gene; Hamsters; Individual; Injection of therapeutic agent; Label; Lead; Learned Helplessness; Maintenance; Mediating; Mental Depression; Mental disorders; Mesocricetus auratus; Modeling; Mood Disorders; Muscimol; Neuronal Plasticity; Neurons; Oxides; Panic Disorder; Post-Traumatic Stress Disorders; Prevention; Psychopathology; Research; Resistance; Social Dominance; Social status; Stress; Stressful Event; Testing; Tracer; Variant; Viral Vector; conditioned fear; designer receptors exclusively activated by designer drugs; dorsal raphe nucleus; experience; improved; interest; neural circuit; neurobiological mechanism; neuromechanism; novel; prevent; public health relevance; relating to nervous system; research study; response; social; social stress; vector

 DESCRIPTION (provided by applicant): Exposure to stressful events is a key factor in the etiology of several mood and anxiety disorders. However, not all individuals exposed to stressful events develop stress-related mental illness, and there is considerable interest in what makes some individuals vulnerable and others resilient. In this proposal, we will investigate the neural substrates and cellular mechanisms controlling resistance to social stress using a social defeat model in Syrian hamsters, called conditioned defeat. Our previous research indicates that neural activity in the infralimbic (IL) and prelimbic (PL) cortex is necessary for the reduced conditioned defeat response exhibited by dominant hamsters. In general, we expect that the maintenance of dominance relationships generates plasticity in specific neural circuits that promotes resistance to conditioned defeat in dominant hamsters. In this proposal, we hypothesize that activation of IL neurons with efferent projections to the basolateral amygdala (BLA) (i.e. IL-to-BLA neural circuit) and PL neurons with efferent projections to the dorsal raphe nucleus (DRN) (i.e. PL-to-DRN neural circuit) regulates resistance to conditioned defeat in dominant hamsters. We will test two specific aims in this proposal. First, we will determine whether elevated defeat- induced neural activation in dominant hamsters occurs within IL-to-BLA and/or PL-to-DRN neural circuits. Second, we will determine whether selective inhibition of IL-to-BLA and/or PL-to-DRN neural circuits prevents resistance to conditioned defeat in dominant hamsters. This line of research will improve our understanding of the neural mechanisms controlling resistance to social stress and will identify novel targets for the prevention and treatment of stress-related mental illness.

 描述（适用提供）：暴露于压力事件是多种情绪和焦虑症的病因的关键因素。但是，并非所有暴露于压力事件的人都会出现与压力有关的精神疾病，并且对使某些人脆弱而其他人抵抗的原因引起了极大的兴趣。在此提案中，我们将使用叙利亚仓鼠中的社会失败模式来调查控制对社会压力的抵抗的神经元底物和细胞机制，称为有条件失败。我们以前的研究表明，对于占主导地位的仓鼠暴露的有条件失败反应的减少是必需的，爆剂（IL）（IL）和前比（PL）皮质是必要的。通常，我们预计维持优势关系会在特定的神经元电路中产生可塑性，从而促进对主导仓鼠的有条件失败的抵抗力。在这项提案中，我们假设通过有效的项目激活IL神经元（bla）（即IL-to-to-bla神经元）和PL神经元，并具有有效的项目对背侧Raphe Nucitus（DRN）（即PL-to-to-to-to-DRN神经元）的有效项目调节对条件抗拒条件的byterals narlymants的抵抗。我们将在该提案中测试两个具体目标。首先，我们将确定在IL-TO-BLA和/或PL-TO-TO-DRN神经元电路内发生升高的失败诱导的神经元激活。其次，我们将确定选择性抑制IL-to-Bla和/或PL-TO-TO-TO-TO-TO-TO-DRN神经元电路是否可以防止在占主导地位的仓鼠中对条件失败的抵抗力。这项研究将提高我们对控制对社会压力抗性的神经元机制的理解，并将确定预防和治疗与压力相关的精神疾病的新目标。

项目成果

Gonadal steroid hormone receptors in the medial amygdala contribute to experience-dependent changes in stress vulnerability.

• DOI: 10.1016/j.psyneuen.2021.105249
• 发表时间: 2021-07
• 期刊: Psychoneuroendocrinology
• 影响因子: 3.7
• 作者: Cooper MA;Clinard CT;Dulka BN;Grizzell JA;Loewen AL;Campbell AV;Adler SG
• 通讯作者: Adler SG

Social Dominance Modulates Stress-induced Neural Activity in Medial Prefrontal Cortex Projections to the Basolateral Amygdala.

• DOI: 10.1016/j.neuroscience.2018.07.042
• 发表时间: 2018-09-15
• 期刊: Neuroscience
• 影响因子: 3.3
• 作者: Dulka BN;Bress KS;Grizzell JA;Cooper MA
• 通讯作者: Cooper MA

Activity of a vmPFC-DRN Pathway Corresponds With Resistance to Acute Social Defeat Stress.

• DOI: 10.3389/fncir.2020.00050
• 发表时间: 2020
• 期刊: Frontiers in neural circuits
• 影响因子: 3.5
• 作者: Grizzell JA;Clarity TT;Graham NB;Dulka BN;Cooper MA
• 通讯作者: Cooper MA