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

项目摘要/摘要 生活常常要求我们在面对危险时保持主动。过马路时，自适应的 对迎面而来的护理者的号角的反应是尽快地越过到另一边。然而，恐惧 可能会产生一种固定的效果，造成一种矛盾的局面，在这种情况下，根深蒂固的防御 为了实现安全，必须压制对危险的抵挡。因此，复杂环境中的适应性应对 环境要求有能力改变过去的防御性反应，转而支持主动的、有问题的 解决行为策略。 主动回避信号(SAA)是一种行为条件反射范式，可以有效地模拟 习得的、解决问题的行动取代由行动引起的先天反应的过程 威胁信号。以往的研究表明，丘脑中线核团起着至关重要的作用。 在这一过程中发挥作用，抑制固定反应，有利于适应性行为 防止令人厌恶的结果的策略。这里提出的工作将扩展这一发现，使用 以抑制冰冻的重组素的关键输出为靶点的化学发生技术 并促进主动回避。我们的主要假设是来自原子核的投射 通过激活边缘区域(如腹侧)的抑制性中间神经元进行前馈抑制 介导厌恶联想表达的海马体和杏仁基底外侧核 记忆，从而产生条件性冻结。成功地执行拟议的研究将建立一个 重要的神经机制，促进行为灵活性和适应性问题解决 威胁。 积极主动的应对方式与内在的控制力和恢复力有关， 暗示了其潜在回路的心理健康相关性。通过剖析这一功能 途径，我们的目标是生成临床前数据，通过提供靶点来加速临床进展 用于尖端的治疗创新。

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.