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

项目概要/摘要 生活常常要求我们在危险面前积极主动。过马路时，自适应 对迎面而来的护理号角的反应是尽快穿过到另一边。然而恐惧 可能会产生一种无法动弹的效果，造成一种自相矛盾的情况，在这种情况下，一种根深蒂固的防御 为了实现安全，必须抑制危险。因此，在复杂的环境中适应性应对 环境要求我们有能力超越防御性反应，转而采取积极主动的、解决问题的方法。 解决行为策略。 信号主动回避（SAA）是一种行为调节范式，可以有效地建模 后天习得的解决问题的行动取代由后天习得的问题引起的本能反应的过程 威胁暗示。过去的研究表明，中线丘脑的团聚核起着至关重要的作用。 在此过程中的作用，抑制固定反应，有利于适应性行为 防止出现令人厌恶的结果的策略。这里提出的工作将通过使用来扩展这一发现 化学遗传学技术针对Reuniens的关键输出，这些输出具有抑制冻结的功能 并促进主动回避。我们的主要假设是来自原子核的投影 通过激活边缘区域（例如腹侧）的抑制性中间神经元来进行前馈抑制 海马体和基底外侧杏仁核，介导厌恶联想的表达 记忆，从而条件性冻结。拟议研究的成功执行将建立 促进行为灵活性和适应性问题解决的重要神经机制 威胁。 积极主动的应对方式与内部控制和复原力相关， 表明其底层电路与心理健康的相关性。通过剖析这个函数 途径，我们的目标是生成临床前数据，通过提供目标来加速临床进展 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.