Regulation of VTA inhibitory synapses by acute and chronic stress

急性和慢性应激对 VTA 抑制性突触的调节

基本信息

  • 批准号:
    9417473
  • 负责人:
  • 金额:
    $ 24.9万
  • 依托单位:
  • 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:
    2016-04-01 至 2020-04-30
  • 项目状态:
    已结题

项目摘要

Modified Project Summary/Abstract Section This project is the R00 phase of a K99/R00 award to be completed in the Department of Pharmacology and Physiology at George Washington University. In this project, I will investigate the role of inhibitory synapses on VTA dopamine neurons in animal models of resilience and susceptibility to stress-induced anhedonia. Dopamine neurons of the ventral tegmental area (VTA) are a crucial part of the brain's reward processing system, and function of these neurons is greatly influenced by stress. In particular, activity of dopamine neurons projecting to the nucleus accumbens has been causally linked to an animal's behavioral response to stress. Inhibitory synapses onto dopamine neurons powerfully modulate their activity, and are thus poised to be a significant mediator of stress's effects on the VTA. In this proposal, I will take a multidisciplinary approach, utilizing electrophysiological, optogenetic, chemogenetic, and behavioral techniques to address the hypothesis that inhibitory synapses onto nucleus accumbens-projecting VTA dopamine neurons are a key determinant of an individual's behavioral responses to stress. I propose two aims, revised from my original K99/R00 application. In the first, I will examine inhibitory synaptic physiology and plasticity onto nucleus accumbens projecting dopamine neurons in mice exhibiting differential responses to two forms of repeated stress: chronic social defeat and subchronic variable stress. In the second, I will examine changes in the strength of two specific inputs (local VTA interneurons and RMTg projections) onto nucleus accumbens-projecting dopamine neurons following chronic social defeat and the ability of chemogenetic manipulation of these inputs to promote resilience to this stressor. These studies hold the potential to contribute significantly to our understanding of how the reward system is altered by stress and may lead to novel avenues for the development of therapeutic treatments for depression and other stress-linked disorders.
修改的项目摘要/摘要部分

项目成果

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Abigail Marie Polter其他文献

Abigail Marie Polter的其他文献

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{{ truncateString('Abigail Marie Polter', 18)}}的其他基金

VTA microcircuit dynamics during chronic stress
慢性应激期间 VTA 微电路动态
  • 批准号:
    10505591
  • 财政年份:
    2020
  • 资助金额:
    $ 24.9万
  • 项目类别:
VTA microcircuit dynamics during chronic stress
慢性应激期间 VTA 微电路动态
  • 批准号:
    10165835
  • 财政年份:
    2020
  • 资助金额:
    $ 24.9万
  • 项目类别:
VTA microcircuit dynamics during chronic stress
慢性应激期间 VTA 微电路动态
  • 批准号:
    10780278
  • 财政年份:
    2020
  • 资助金额:
    $ 24.9万
  • 项目类别:
VTA microcircuit dynamics during chronic stress
慢性应激期间 VTA 微电路动态
  • 批准号:
    10356928
  • 财政年份:
    2020
  • 资助金额:
    $ 24.9万
  • 项目类别:
VTA microcircuit dynamics during chronic stress
慢性应激期间 VTA 微电路动态
  • 批准号:
    10577777
  • 财政年份:
    2020
  • 资助金额:
    $ 24.9万
  • 项目类别:
Regulation of VTA inhibitory synapses by acute and chronic stress
急性和慢性应激对 VTA 抑制性突触的调节
  • 批准号:
    9041686
  • 财政年份:
    2015
  • 资助金额:
    $ 24.9万
  • 项目类别:

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