Norepinephrine tunes prefrontal-thalamic circuitry to modulate avoidance behavior

去甲肾上腺素调节前额丘脑回路以调节回避行为

基本信息

  • 批准号:
    10586051
  • 负责人:
  • 金额:
    $ 18.59万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-03-07 至 2025-02-28
  • 项目状态:
    未结题

项目摘要

Norepinephrine tunes prefrontal-thalamic circuitry to modulate avoidance behavior Abstract Anxiety disorders are the most common mental illness in the U.S., affecting ~18% of the population. However, the underlying mechanisms associated with anxiety remain elusive. Recent evidence has identified the medial prefrontal cortex (mPFC) as a crucial regulator of anxiety and disruption of mPFC-mediated executive functions in anxiety disorders. On the other hand, norepinephrine (NE) has long been associated with stress and anxiety. A morphological study showed a higher density of dopamine beta-hydroxylase (DBH) varicosities in the PFC than in other cortices. However, how the mPFC executes top-down control over other brain regions to regulate anxiety-related approach-avoidance behavior and whether and how this is modulated by norepinephrine (NE) remain unclear. This project will test the innovative concept that mPFC – paraventricular thalamus (mPFC-PVT) circuit is an important previously overlooked target for anxiety and decision-making. Our pilot study suggests that chemogenetically inhibiting mPFC-PVT pathway with DREADD viral victor significantly increased the time spent in the open arm of the elevated plus-maze, indicating a reduction in anxiety-related avoidance behavior. We thus hypothesize that mPFC-pPVT neurons are active during the exploration of aversive environments, which drives avoidance behavior and elicits anxiety-dependent behaviors. We will explore the extent that prefrontal NE signaling modulates this effect. We will investigate the communication between these two regions by using calcium imaging, a detailed DeepLabCut analysis of animal’s behavior (Aim 1) combined with a G- protein-coupled receptor (GPCR) Activation-Based Norepinephrine (GRAB-NE) sensor (Aim 2) for anxiety-like behavior. The GRAB-NE will allow us to monitor prefrontal NE dynamics in real-time in free-behaving animals. The DeepLabCut™ will provide a detailed analysis of an animal’s posture with a sub-millisecond temporal resolution that could be used to determine an animal’s emotional state change. In summary, we address these conceptually innovative questions using state-of-the-art methods, which allow for precise, causal interrogation into the role of this circuit both in vivo and ex vivo in a projection-specific manner.
去甲肾上腺素调节前额叶-丘脑回路来调节回避行为

项目成果

期刊论文数量(0)
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专利数量(0)

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Wen-Jun Gao其他文献

Wen-Jun Gao的其他文献

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{{ truncateString('Wen-Jun Gao', 18)}}的其他基金

Corticothalamic control of social motivation
皮质丘脑控制社会动机
  • 批准号:
    10529968
  • 财政年份:
    2022
  • 资助金额:
    $ 18.59万
  • 项目类别:
Norepinephrine tunes prefrontal-thalamic circuitry to modulate avoidance behavior
去甲肾上腺素调节前额丘脑回路以调节回避行为
  • 批准号:
    10451927
  • 财政年份:
    2022
  • 资助金额:
    $ 18.59万
  • 项目类别:
Corticothalamic control of social motivation
皮质丘脑控制社会动机
  • 批准号:
    10661763
  • 财政年份:
    2022
  • 资助金额:
    $ 18.59万
  • 项目类别:
Behavioral effects of igsf9b in the prefrontal cortex
igsf9b 对前额皮质的行为影响
  • 批准号:
    10054717
  • 财政年份:
    2020
  • 资助金额:
    $ 18.59万
  • 项目类别:
Role of prefrontal cortical dopamine in aggression
前额皮质多巴胺在攻击行为中的作用
  • 批准号:
    9281915
  • 财政年份:
    2016
  • 资助金额:
    $ 18.59万
  • 项目类别:
Role of prefrontal cortical dopamine in aggression
前额皮质多巴胺在攻击行为中的作用
  • 批准号:
    9153019
  • 财政年份:
    2016
  • 资助金额:
    $ 18.59万
  • 项目类别:
HIV gp120 and Prefrontal Cortical Function
HIV gp120 和前额皮质功能
  • 批准号:
    8434874
  • 财政年份:
    2012
  • 资助金额:
    $ 18.59万
  • 项目类别:
HIV gp120 and Prefrontal Cortical Function
HIV gp120 和前额皮质功能
  • 批准号:
    8331029
  • 财政年份:
    2012
  • 资助金额:
    $ 18.59万
  • 项目类别:
Antipsychotic Mechanisms of mGluR Agonists in the MK-801 Model of Schizophrenia
mGluR 激动剂在 MK-801 精神分裂症模型中的抗精神病机制
  • 批准号:
    8268507
  • 财政年份:
    2009
  • 资助金额:
    $ 18.59万
  • 项目类别:
Development of NMDAR hypofunction and cognitive deficits
NMDAR 功能减退和认知缺陷的发展
  • 批准号:
    8898214
  • 财政年份:
    2009
  • 资助金额:
    $ 18.59万
  • 项目类别:

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肾上腺素能药物治疗AD疗效的临床前试验
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    2009
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  • 批准号:
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甲基苯丙胺肾上腺素药物:门诊试验
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    2004
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