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Balancing excitatory and inhibitory LHb signaling underlying stress

平衡潜在压力的兴奋性和抑制性 LHb 信号

基本信息

批准号：
10426102
负责人：
Dillon McGovern
金额：
$ 3.93万
依托单位：
UNIVERSITY OF COLORADO
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：
2021-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10426102
关键词：
Address Affect Animals Anxiety Behavior Behavior Control Behavioral Binding Biosensor Brain region Buffers Chemicals Cognitive Therapy Complex Data Development Dorsal Equilibrium Foundations Glutamates Goals Habenula Human Hyperactivity Image Individual Lateral Link Literature Mediating Mental Depression Modeling Mood Disorders Mus Neurobiology Neurons Neurosciences Neurotransmitters Pathology Pathway interactions Play Presynaptic Terminals Process Rewards Rodent Model Role Severities Signal Transduction Stress Stressful Event Structure Techniques Testing Therapeutic Training United States Ventral Tegmental Area Viral anxiety-like behavior comorbidity depressive behavior depressive symptoms experience experimental study innovation motivated behavior neurochemistry new therapeutic target optogenetics prevent psychologic recruit relating to nervous system resilience stress related disorder stress resilience stressor two photon microscopy

项目摘要

PROJECT SUMMARY Over 40 millions individuals in the United States are impacted by stress related disorders, that are highly comorbid with mood disorders such as anxiety and depression. Cognitive behavioral therapy and decades of animal literature has established that reinstating a sense of autonomy or behavioral control over a stressful experience can buffer many of the psychological and behavioral impacts of stress and reduce the severity of depressive and anxiety-like behaviors. However, it is not entirely known which neurochemical pathways are recruited by behavioral control to facilitate or hinder this stress resilience. Understanding how neurochemical signaling dynamics change following stress (with and without behavioral control) and identifying which projections are responsible for these changes is a foundational step in developing therapeutics for stress related disorders. To address this, I will implement a rodent model of stressor controllability to 1) identify how neurochemical signaling dynamics change following behavioral control, in a brain region highly implicated in mediating the effects of stress and 2) manipulate neurochemical-specific projections to this region that are implicated in these changes to identify their involvement in stressor controllability. The goal of the proposed project is to determine how behavioral control impacts discrete neurochemical signaling specifically between the lateral habenula (LHb) and the ventral tegmental area (VTA), two interacting brain regions that play causal roles in both stress and motivated behavior. The successful completion of these aims will address mechanistically how behavioral control influences LHb neurochemical signaling and test the hypothesis that the VTA glutamate → LHb pathway contributes to behavioral deficits following stress experience in the absence of behavioral control.

项目摘要在美国，超过4000万人受到与压力有关的疾病的影响，这些疾病的发病率很高。与焦虑和抑郁等情绪障碍共病。认知行为疗法和数十年的动物文献已经确定，恢复自主意识或对压力的行为控制，经验可以缓冲压力对心理和行为的许多影响，抑郁和类似焦虑的行为。然而，尚不完全清楚哪些神经化学途径是通过行为控制来促进或阻碍这种压力恢复力。了解神经化学物质信号动力学在压力（有和没有行为控制）后发生变化，并确定是开发压力疗法的基础步骤相关疾病。为了解决这个问题，我将实现一个啮齿动物模型的压力可控性，以1）确定如何在行为控制之后，神经化学信号动力学发生变化，在大脑区域中，调解压力的影响和2）操纵神经化学特异性投射到这个区域，参与这些变化，以确定其参与压力可控性。建议的目标该项目旨在确定行为控制如何影响离散神经化学信号，特别是在外侧缰核（LHb）和腹侧被盖区（VTA），这两个相互作用的大脑区域，在压力和动机行为中的作用。这些目标的成功实现将解决行为控制如何影响LHb神经化学信号传导，并检验以下假设：腹侧被盖区谷氨酸→ LHb通路导致应激后的行为缺陷，缺乏行为控制。