Prefrontal amygdala interactions in fear conditioning

前额杏仁核在恐惧调节中的相互作用

基本信息

批准号：
9918979
负责人：
Gregory J Quirk
金额：
$ 37.5万
依托单位：
UNIVERSITY OF PUERTO RICO MED SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9918979
关键词：
Amygdaloid structure Anxiety Behavior Behavioral Conflict (Psychology)Corpus striatum structure Cues Decision Making Dependovirus Detection Electrophysiology (science)Equilibrium Failure Female Fiber Food Food Safety Fright Human Immunohistochemistry Instruction Lasers Light Maps Mediating Mental Depression Methods Modeling Monitor Motivation National Institute of Mental Health Neurons Pathologic Pattern Phase Phenotype Photometry Principal Investigator Process Rattus Reaction Research Research Domain Criteria Rewards Rodent Silicon Social Interaction Stimulus Structure Subgroup Syndrome Technology Testing Training Work activity marker addiction anxious behavior approach avoidance behavior base behavior test behavioral phenotyping behavioral response conditioned fear experimental study hedonic interest male motivated behavior neural circuit novel novel strategies optogenetics programs relating to nervous system response social student training trait translational study

项目摘要

Pursuit of reward and avoidance of threat are two major behavioral motivators. Failure to balance these motivations results in maladaptive decisions and may underlie various pathological conditions. The sustained threat construct of the NIMH Research Domain Criteria (RDoC) includes avoidance, conflict detection, and perseverative behaviors. Sustained threat reactions interfere with the pursuit of rewarding activities that can decrease social interactions and trigger depression. Little is known about how decisions guide behavior during approach-avoidance conflict. The first phase of this MERIT shifted our focus from Pavlovian fear conditioning to active avoidance, exploring how prefrontal-amygdala-striatal circuits express and extinguish active avoidance. For the second MERIT phase, we have developed a new task that maximizes approach-avoidance conflict within a timed cue encounter that pits active avoidance against the pursuit of food. The new approach-avoidance conflict task has revealed three distinct behavioral phenotypes: 1) food-preferring rats that pursue food throughout the tone with little or no avoidance; 2) avoidance-preferring rats which avoid throughout the tone with little or no food-seeking; and 3) timers which seek food early in the tone and avoid later, thereby maximizing both access to food and safety. We will capitalize on these unique behavioral phenotypes to characterize the circuits mediating approach- avoidance decisions, using electrophysiological, immunohistochemical, and optogenetic methods. We will use both male and female rats in all our aims. Aim 1 will use immunohistochemistry combined with electrophysiology and fiber photometry to identify the circuits involved in conflict decision making. Aim 2 will test the circuits identified in Aim 1 with optogenetic manipulations. Aim 3 will assess the power of this task to identify new multi-dimensional behavioral phenotypes integrating conflict strategies with anxiety and social interactions. This research program will enable us to characterize decision-making circuits underlying different strategies for resolving approach-avoidance conflict. RELEVANCE (See instructions): Failure to balance pursuit of reward and avoidance of threat results in maladaptive decisions and pathological conditions including anxiety and depression. Using a novel rodent task that maximizes approach-avoidance conflict, we will characterize the circuits mediating approach-avoidance decisions using electrophysiological, immunohistochemical, and optogenetic methods. This research program will enable us to characterize circuits for resolving approach-avoidance conflict.

追求奖励和避免威胁是两个主要的行为动机。无法平衡这些动机会导致适应不良的决策，并可能是各种病理状况的基础。这 NIMH研究领域标准（RDOC）的持续威胁结构包括避免，冲突检测和毅力行为。持续威胁反应干扰了追求奖励可以减少社交互动并触发抑郁症的活动。关于决策的了解知之甚少指导避免冲突期间的行为。这个优点的第一阶段将我们的重点从帕夫洛维亚恐惧调节以进行主动避免，探索前额叶 - 杏仁核电路如何表达并扑灭积极的回避。对于第二个优异阶段，我们开发了一项新任务在定时的提示遭遇中最大化避免接近 - 避免冲突追求食物。新的避免进程冲突的任务揭示了三种不同的行为表型：1）偏爱食物的大鼠，在整个语气中追求食物，几乎没有回避； 2）避免偏爱的大鼠，避免在整个语气中，几乎没有寻求食物； 3）计时器在酸味的早期寻求食物，并避免以后，从而最大程度地获得食物和安全性。我们将利用这些独特的行为表型来表征介导方法的电路避免决定，使用电生理，免疫组织化学和光遗传学方法。我们将在我们的所有目标中都使用男性和雌性老鼠。 AIM 1将使用免疫组织化学结合电生理学和光纤光度法确定冲突决策所涉及的电路。 AIM 2意志测试AIM 1中通过光遗传操作确定的电路。 AIM 3将评估这项任务的力量确定新的多维行为表型将冲突策略与焦虑整合到社交互动。该研究计划将使我们能够表征依据的决策电路解决避免进近冲突的不同策略。相关性（请参阅说明）：未能平衡追求奖励和避免威胁会导致适应不良的决定和病理状况，包括焦虑和抑郁。使用最大化的新型啮齿动物任务避免进近冲突，我们将表征介导方法避免方法的电路使用电生理，免疫组织化学和光遗传学方法。该研究计划将使我们能够表征解决避免进近冲突的电路。