Neural Circuits Controlling Resiliency in Dominant Animals

控制优势动物弹性的神经回路

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：暴露于压力事件是多种情绪和焦虑障碍病因的关键因素。然而，并非所有暴露于压力事件的人都会患上与压力相关的精神疾病，并且人们对某些人的精神疾病的成因非常感兴趣。在本提案中，我们将使用叙利亚仓鼠的社会失败模型（称为条件失败）来研究控制对社会压力的抵抗力的神经基质和细胞机制。（IL）和前边缘（PL）皮层对于优势仓鼠表现出的条件性失败反应的减少是必要的。一般来说，我们预计优势关系的维持会在特定的神经回路中产生可塑性，从而促进优势仓鼠对条件性失败的抵抗力。提议，我们追求通过传出投射到基底外侧杏仁核（BLA）（即 IL-to-BLA 神经回路）激活 IL 神经元，并通过传出投射激活 PL 神经元中缝背核（DRN）（即 PL-to-DRN 神经回路）的投射调节优势仓鼠对条件性失败的抵抗力。我们将测试该提议中的两个具体目标。在优势仓鼠中，IL-to-BLA 和/或 PL-to-DRN 神经回路内发生第二，我们将确定是否选择性抑制 IL-to-BLA 和/或 PL-to-DRN。神经回路可以防止占主导地位的仓鼠对条件性失败的抵抗力，这一系列研究将提高我们对控制社会压力抵抗力的神经机制的理解，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

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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

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Matthew A Cooper其他文献

Design, synthesis, conformational analysis and nucleic acid hybridisation properties of thymidyl pyrrolidine-amide oligonucleotide mimics (POM).

胸苷基吡咯烷酰胺寡核苷酸模拟物 (POM) 的设计、合成、构象分析和核酸杂交特性。

DOI：
10.1039/b306156f
发表时间：
2003
期刊：
Organic & biomolecular chemistry
影响因子：
3.2
作者：
David T Hickman;T. Tan;J. Morral;Paul M King;Matthew A Cooper;Jason Micklefield
通讯作者：
Jason Micklefield