The role of medial prefrontal cortex in active avoidance behavior

内侧前额叶皮层在主动回避行为中的作用

基本信息

  • 批准号:
    8254128
  • 负责人:
  • 金额:
    $ 5.11万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-12-20 至 2014-12-19
  • 项目状态:
    已结题

项目摘要

Excessive fear, a central component of many anxiety disorders, can have deleterious effects on both psychological and physical wellbeing. Treatments for anxiety disorders often endeavor to supplant fear-based reactions with instrumental actions that can be thought of as active coping strategies. Thus, the capacity to transition from reactive fear to active coping has clear clinical significance ¿ understanding the biological basis of this process could provide a sound platform for advancements in the treatment of anxiety-related psychopathologies. Signaled active avoidance learning can offer important insights into this transitional process. In this form of conditioning, subjects are trained to avoid an unconditioned stimulus (US) by performing an instrumental action when a predictive conditioned stimulus (CS) is presented. Interestingly, an initial Pavlovian fear reaction, freezing, predominates through early training and constrains the development of active behaviors during CS presentation. Over the course of learning freezing is suppressed, allowing active avoidance responses to become manifest. It is this very suppression of freezing that this proposal seeks to examine, as it represents a compelling model of the transition from reactive to active behavioral states. A neurobiological understanding of this phenomenon could shed light on the substrates of anxiety and resilience, and thus has ample translational potential. The ventromedial prefrontal cortex (vmPFC) is involved in the suppression of maladaptive or inappropriate behaviors, whereas the central nucleus of the amygdala (CeA) is crucial for CS evoked freezing. vmPFC cells form synapses on the neurons that comprise the intercalated cell masses of the amygdala (ITC), which are an inhibitory population that in turn project to the cells of the CeA. The basic hypothesis that this proposal will pursue is that vmPFC exerts feed-forward inhibition on CeA during signaled avoidance learning, thus suppressing CS-evoked freezing and allowing the subject to execute an instrumental avoidance response when the CS is presented. To explore this hypothesis, three specific aims are proposed: 1) to ascertain the role of vmPFC and Cea in the suppression of freezing during signaled avoidance learning, 2) to identify the role of the ITC, and of the vmPFC projection to those neurons, and 3) to determine the timing and nature of vmPFC involvement in the suppression of freezing. Experiments proposed under the first two aims will involve traditional lesion techniques, while the final aim will be explored using the light-activated inhibitory molecule Archaerhodopsin-3. This blend of conventional (lesion) and cutting edge (optogenetic) methodologies will allow for a detailed and precise exploration of the proposed model, thus shedding light on the neuroboiogical substrates of a clinically relevant behavioral phenomenon.
过度恐惧是许多焦虑症的核心组成部分,可能会对心理和身体健康产生有害影响。焦虑症的治疗通常试图用可以被认为是积极应对策略的工具性行动来取代基于恐惧的反应。因此,从反应性恐惧转变为积极应对的能力具有明显的临床意义。了解这一过程的生物学基础可以为焦虑相关精神疾病的治疗提供一个良好的平台。 有信号的主动回避学习可以为这一过渡过程提供重要的见解。在这种形式的条件反射中,受试者被训练成在出现预测性条件刺激(CS)时通过执行工具动作来避免无条件刺激(US)。有趣的是,最初的巴甫洛夫恐惧反应,冻结,在早期训练中占主导地位,并在CS陈述期间限制积极行为的发展。在学习过程中,冻结被抑制,允许主动回避反应变得明显。这项提议试图考察的正是对冻结的抑制,因为它代表了从被动行为状态到主动行为状态的令人信服的转变模型。对这一现象的神经生物学理解可以揭示焦虑和韧性的根源,因此具有很大的翻译潜力。 腹内侧前额叶皮质(VmPFC)参与抑制不适应或不当行为,而杏仁中央核(CEA)对CS诱发的冰冻起关键作用。VmPFC细胞在构成杏仁核(ITC)插入细胞团的神经元上形成突触,后者是一个抑制性群体,反过来投射到CEA细胞。这一提议的基本假设是,vmPFC在信号回避学习过程中对CEA施加前馈抑制,从而抑制CS诱发的冻结,并允许被试在CS呈现时执行工具性回避反应。为了探索这一假说,我们提出了三个具体的目标:1)确定vmPFC和CEA在信号回避学习中抑制冻结的作用;2)确定ITC的作用和vmPFC向这些神经元的投射;3)确定vmPFC参与抑制冻结的时间和性质。在前两个目标下提出的实验将涉及传统的损伤技术,而最终目标将使用光激活的抑制分子古紫质-3来探索。这种传统(损伤)和尖端(光遗传)方法的结合将允许对所提出的模型进行详细和精确的探索,从而揭示临床相关行为现象的神经生物学基础。

项目成果

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Justin M Moscarello其他文献

Justin M Moscarello的其他文献

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{{ truncateString('Justin M Moscarello', 18)}}的其他基金

Dissecting the role of the bed nucleus of the stria terminalis in avoidant behavior
剖析终纹床核在回避行为中的作用
  • 批准号:
    10457413
  • 财政年份:
    2021
  • 资助金额:
    $ 5.11万
  • 项目类别:
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
  • 财政年份:
    2021
  • 资助金额:
    $ 5.11万
  • 项目类别:
Dissecting the role of the bed nucleus of the stria terminalis in avoidant behavior
剖析终纹床核在回避行为中的作用
  • 批准号:
    10303895
  • 财政年份:
    2021
  • 资助金额:
    $ 5.11万
  • 项目类别:
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:
    10354461
  • 财政年份:
    2021
  • 资助金额:
    $ 5.11万
  • 项目类别:
The role of medial prefrontal cortex in active avoidance behavior
内侧前额叶皮层在主动回避行为中的作用
  • 批准号:
    8411448
  • 财政年份:
    2011
  • 资助金额:
    $ 5.11万
  • 项目类别:
Dopamine terminal regions interact as a function of motivation and reinforcement
多巴胺末端区域作为动机和强化的函数相互作用
  • 批准号:
    7673119
  • 财政年份:
    2009
  • 资助金额:
    $ 5.11万
  • 项目类别:

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