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Hippocampus, synaptic plasticity and anxiety vulnerability

海马、突触可塑性和焦虑脆弱性

基本信息

批准号：
9788182
负责人：
Kevin C.H. Pang
金额：
--
依托单位：
VA NEW JERSEY HEALTH CARE SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2019-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9788182
关键词：
Affect Agonist Anxiety Anxiety Disorders Attenuated Avoidance Learning Basic Science Behavior Behavioral Behavioral inhibition Brain Brain-Derived Neurotrophic Factor Cost Savings Cycloserine Development Disease Effectiveness Electric Stimulation Environment Etiology Evoked Potentials Functional disorder General Population Health Hippocampus (Brain)Human Impairment Inbred Strain Inbred WKY Rats Individual Knowledge Lateral Lead Learning Long-Term Potentiation Medial Medical N-Methyl-D-Aspartate Receptors N-Methylaspartate Neurotrophic Tyrosine Kinase Receptor Type 2 Opiate Addiction Opioid Opioid Antagonist Opioid Receptor Opioid agonist Patients Perforant Pathway Pharmaceutical Preparations Post-Traumatic Stress Disorders Psychiatry Psychopathology Risk Risk Factors Services Sprague-Dawley Rats Stress Synaptic plasticity System Temperament Testing Time Training Veterans War Work anxiety-related disorders brain abnormalities brain dysfunction combat dentate gyrus medical specialist mu opioid receptors neurotrophic factor prevent public health relevance stressor therapy development treatment of anxiety disorders

项目摘要

DESCRIPTION (provided by applicant): Risk factors for anxiety disorder are important in determining who ultimately develops the disorder. However, our understanding of risk factors is rudimentary. Identification of the mechanisms of risk factors would be a step forward in understanding the etiology of anxiety disorders. Reduced hippocampal volume, dysfunction of the brain-derived neurotrophin factor (BDNF) system and behavioral inhibition temperament are three anxiety risk factors identified in humans. The risk factor of reduced hippocampal volume is associated with impaired hippocampal-dependent learning, suggesting impaired hippocampal synaptic plasticity in individuals at risk. BDNF is important for synaptic plasticity. Thus, we hypothesize that impaired hippocampal synaptic plasticity may underlie the risk factors of both reduced hippocampal volume and BDNF dysfunction. The Wistar Kyoto (WKY) rat is an inbred strain that is stress sensitive, has a reduced hippocampal volume compared to the outbred Sprague Dawley (SD) rat, has an abnormal BDNF system and expresses a behavioral inhibition. In addition, WKY rats acquire active avoidance to a greater and more persistent degree than SD rats. Abnormal avoidance is a core feature of all anxiety disorders, and the development of abnormal avoidance parallels the trajectory of PTSD (cluster C). Thus, the proposed studies will test whether impaired synaptic plasticity in the hippocampus contributes to the development of abnormal avoidance learning in the presence and absence of behavioral inhibition temperament. Four aims are proposed. Aim 1 will determine whether BDNF-induced synaptic plasticity is impaired in the hippocampus of WKY rats and if NMDA and BDNF agonists can attenuate these impairments. Aim 2 will investigate the effects of drugs acting on NMDA and BDNF-TrkB receptors on avoidance learning. Aim 3 will determine if opioid-dependent LTP in the hippocampus is impaired in WKY rats. Opioid-dependent LTP does not require NMDA or TrkB receptors. Aim 4 will investigate whether drugs acting on opioid receptors can affect the development of abnormal avoidance responding. Because opioid-dependent LTP is independent of NMDA and TrkB receptors, the comparison of opioid LTP to NMDA- and BDNF-LTP will determine whether the development of abnormal avoidance requires impairment of a specific type of LTP (i.e., NMDA) or if impairment to any of the various forms of LTP in the hippocampus can lead to the development of abnormal avoidance. The proposed studies will start to elucidate the mechanisms and interactions of three risk factors for anxiety disorders. Understanding the etiology of anxiety disorders and mechanisms of risk factors will help in the development of treatments. This is especially important to the health of veterans because a significant number of veterans are likely to develop anxiety-related disorders as a result of the extreme stress associated with combat service.

描述（由申请人提供）：

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Paired-housing selectively facilitates within-session extinction of avoidance behavior, and increases c-Fos expression in the medial prefrontal cortex, in anxiety vulnerable Wistar-Kyoto rats.

在焦虑易感的 Wistar-Kyoto 大鼠中，配对饲养选择性地促进会话内回避行为的消失，并增加内侧前额叶皮质中的 c-Fos 表达。

DOI：
10.1016/j.physbeh.2016.05.044
发表时间：
2016
期刊：
Physiology & behavior
影响因子：
2.9
作者：
Smith,IanM;Pang,KevinCH;Servatius,RichardJ;Jiao,Xilu;Beck,KevinD
通讯作者：
Beck,KevinD

Corrigendum: Use of the Exponential and Exponentiated Demand Equations to Assess the Behavioral Economics of Negative Reinforcement.

勘误表：使用指数和指数需求方程评估负强化的行为经济学。

DOI：
10.3389/fnins.2017.00376
发表时间：
2017
期刊：
Frontiers in neuroscience
影响因子：
4.3
作者：
Fragale,JenniferEC;Beck,KevinD;Pang,KevinCH
通讯作者：
Pang,KevinCH

Neurocognitive and Fine Motor Deficits in Asymptomatic Adolescents during the Subacute Period after Concussion.

脑震荡后亚急性期无症状青少年的神经认知和精细运动缺陷。

DOI：
10.1089/neu.2017.5314
发表时间：
2018
期刊：
Journal of neurotrauma
影响因子：
4.2
作者：
Servatius,RichardJ;Spiegler,KevinM;Handy,JustinD;Pang,KevinCH;Tsao,JackW;Mazzola,CatherineA
通讯作者：
Mazzola,CatherineA

Danger and safety signals independently influence persistent pathological avoidance in anxiety-vulnerable Wistar Kyoto rats: A role for impaired configural learning in anxiety vulnerability.

危险和安全信号独立影响焦虑易感 Wistar京都大鼠的持续病理性回避：配置学习受损在焦虑脆弱性中的作用。