权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Role of amygdala inhibitory circuit neuromodulation in stress disorders

杏仁核抑制回路神经调节在应激障碍中的作用

基本信息

批准号：
10657332
负责人：
JEFFREY G TASKER
金额：
--
依托单位：
SOUTHEAST LOUISIANA VETERANS HEALTH CARE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10657332
关键词：
Adrenergic Receptor Amygdaloid structure Arousal Behavioral Paradigm Brain Cells Chemosensitization Cholecystokinin Cognitive Complex Designer Drugs Development Emotional Equilibrium Excitatory Synapse Exposure to Extinction Feeling suicidal Financial Hardship Foundations Fright Genetic Genetically Engineered Mouse Health Interneurons Learning Light Link Measures Mediating Memory Modeling Mus Neuronal Plasticity Neurons Norepinephrine Output Parvalbumins Pathologic Pathology Pattern Phase Play Post-Traumatic Stress Disorders Process Psychopathology Regulation Risk Factors Role Signal Transduction Slice Societies Source Stereotyping Stream Stress Structure Suicide Synapses Testing Trauma Viral alcohol use disorder behavior test cell type desensitization experimental study fear memory gamma-Aminobutyric Acid genetic approach in vivo insight locus ceruleus structure memory consolidation memory process mouse model nerve supply neural neural circuit neurochemistry neuroregulation neurotransmission noradrenergic optogenetics patch clamp postsynaptic pre-clinical preclinical study presynaptic receptor response sensory integration stress disorder suicidal synaptic inhibition traumatic stress

项目摘要

Project Title: Role of amygdala inhibitory circuit neuromodulation in stress disorders Project Summary Traumatic stress exposure can lead to long-term stress disorders and represents a considerable risk factor for suicide. Stress disorders such as posttraumatic stress disorder (PTSD) and alcohol use disorder have significant links with suicidality and are characterized by plasticity of neural circuits and neurochemical signaling in the amygdala, particularly in the basolateral complex of the amygdala (BLA). The BLA integrates neural inputs from multiple sources and assigns emotional valence to information by establishing distinct streams of information outflow. BLA circuits process inputs to form emotional memories based on the excitation/inhibition balance set by the relative excitatory and inhibitory synaptic inputs to the principal output neurons of the BLA. While potentiation at excitatory synapses is the foundation of memory formation, inhibitory circuits regulate the excitation/inhibition balance to control synaptic potentiation, and neuromodulatory signals tune the synaptic interactions. Noradrenergic modulation is thought to signal arousal and contribute significantly to the emotional salience of information processed in the amygdala. Our preliminary preclinical findings in mice suggest that norepinephrine (NE) exerts robust regulatory control over GABAergic parvalbumin (PV) and cholecystokinin (CCK) inhibitory inputs to the BLA principal neurons, and that this control is compromised following traumatic stress exposure. We propose to characterize the noradrenergic modulation of PV and CCK synaptic inputs to the BLA principal neurons, and to define the role of noradrenergic modulation of synaptic inhibition in BLA- mediated fear memory formation. We will target the noradrenergic afferent regulation of PV and CCK interneuronal circuits using chemogenetic and optogenetic strategies. We will interrogate local PV and CCK interneuron inhibitory synaptic signaling in the BLA for noradrenergic neuromodulation using patch clamp recordings in slices of amygdala. We will use behavioral paradigms to determine the role of the noradrenergic modulation of BLA inhibitory circuits in fear consolidation and extinction. Finally, we will test for traumatic stress- induced plasticity of the noradrenergic modulation of inhibitory circuits and the PV and CCK circuit regulation of fear learning. These studies together will reveal the mechanisms of the noradrenergic modulation of BLA circuits and provide important insights into the role(s) of distinct perisomatic inhibitory circuits in the control of BLA- dependent fear memory formation, as well as into how these circuits are disrupted by traumatic stress exposure.

项目名称：杏仁核抑制回路神经调节在应激障碍中的作用

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Gq neuromodulation of BLA parvalbumin interneurons induces burst firing and mediates fear-associated network and behavioral state transition in mice.

DOI：
10.1038/s41467-022-28928-y
发表时间：
2022-03-11
期刊：
Nature communications
影响因子：
16.6
作者：
Fu X;Teboul E;Weiss GL;Antonoudiou P;Borkar CD;Fadok JP;Maguire J;Tasker JG
通讯作者：
Tasker JG

Stress-induced glucocorticoid desensitizes adrenoreceptors to gate the neuroendocrine response to somatic stress in male mice.

压力诱导的糖皮质激素使肾上腺受体脱敏，以对雄性小鼠的躯体应激反应构成神经内分泌反应。

DOI：
10.1016/j.celrep.2022.111509
发表时间：
2022-10-18
期刊：
CELL REPORTS
影响因子：
8.8
作者：
Jiang, Zhiying;Chen, Chun;Weiss, Grant L.;Fu, Xin;Stelly, Claire E.;Sweeten, Brook L. W.;Tirrell, Parker S.;Pursell, India;Stevens, Carly R.;Fisher, Marc O.;Begley, John C.;Harrison, Laura M.;Tasker, Jeffrey G.
通讯作者：
Tasker, Jeffrey G.