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Title: The thalamic nucleus reuniens mediates the transition from reactive to proactive defensive behavior via feedforward inhibition

Title: The thalamic nucleus reuniens mediates the transition from reactive to proactive defensive behavior via feedforward inhibition
标题:丘脑团聚核通过前馈抑制介导从反应性防御行为到主动防御行为的转变
批准号:
10538605
负责人:
Justin M Moscarello
金额:
$7.15万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-12-10 至 2023-11-30

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PROJECT SUMMARY/ABSTRACT Life often requires us to be proactive in the face of danger. When crossing the road, the adaptive response to the horn of an oncoming care is to cross to the other side as quickly as possible. Yet fear can have an immobilizing effect, creating a paradoxical situation in which a deeply engrained defense against danger must be suppressed in order to achieve safety. Thus, adaptive coping in a complex environment necessitates the ability to move past defensive reactions in favor of proactive, problem- solving behavioral strategies. Signaled active avoidance (SAA) is a behavioral conditioning paradigm that effectively models the process by which a learned, problem-solving action replaces the innate reactions elicited by a threatening cue. Past work suggests that the nucleus reuniens of the midline thalamus plays a crucial role in this process, acting to suppress immobilizing responses in favor of an adaptive behavioral strategy that prevents an aversive outcome. Work proposed here will extend this finding by using chemogenetic techniques to target the crucial outputs of the reuniens that function to suppress freezing and facilitate active avoidance. Our primary hypothesis is that projections from the nucleus reuniens engage feedforward inhibition by activating inhibitory interneurons in limbic regions, such as the ventral hippocampus and the basolateral amygdala, that mediate the expression of aversive associative memory and thus conditioned freezing. Successful execution of the proposed studies will establish an important neural mechanism that promotes behavioral flexibility and adaptive problem solving under threat. A proactive style of coping is associated with an internal locus of control and resilience, suggesting the mental health relevance of its underlying circuitry. By dissecting the function of this pathway, our goal is to generate preclinical data that hastens clinical advancement by providing targets for cutting-edge therapeutic innovations.
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Dissecting the role of the bed nucleus of the stria terminalis in avoidant behavior
  • 批准号:
    10457413
  • 项目类别:
  • 资助金额:
    $18.37万
  • 财政年份:
    2021
  • 负责人:
    Justin M Moscarello
  • 依托单位:
Dissecting the role of the bed nucleus of the stria terminalis in avoidant behavior
  • 批准号:
    10303895
  • 项目类别:
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  • 财政年份:
    2021
  • 负责人:
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  • 依托单位:
Title: The thalamic nucleus reuniens mediates the transition from reactive to proactive defensive behavior via feedforward inhibition
  • 批准号:
    10354461
  • 项目类别:
  • 资助金额:
    $7.17万
  • 财政年份:
    2021
  • 负责人:
    Justin M Moscarello
  • 依托单位:
The role of medial prefrontal cortex in active avoidance behavior
  • 批准号:
    8411448
  • 项目类别:
  • 资助金额:
    $5.22万
  • 财政年份:
    2011
  • 负责人:
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