A Long-range Recurrent Neural Network Mediates Threat Induced Innate Sensorimotor Integrations

远程循环神经网络介导威胁诱发的先天感觉运动整合

• 批准号: 10539071
• 负责人: Qian-Quan Sun
• 金额: $ 21.68万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10539071
• 关键词: Amygdaloid structure; Animals; Anxiety; Attention; Aversive Stimulus; Behavior; Charge; Code; Dangerousness; Data; Decision Making; Detection; Emotional; Emotions; Environment; Feedback; Freezing; Fright; Goals; Health; Height; Impairment; Instinct; Knowledge; Lateral; Life; Link; Longevity; Loudness; Mediating; Memory; Mental disorders; Modeling; Motor Cortex; Neurobiology; Neurons; Noise; Output; Pain; Pattern; Persons; Phobias; Play; Process; Prosencephalon; Recurrence; Research; Role; Scheme; Sensory; Signal Transduction; Stimulus; Sweating; Symptoms; Synapses; Syndrome; Testing; Thalamic structure; anxiety-related disorders; avoidance behavior; behavioral response; member; multisensory; neuromechanism; novel; post-traumatic stress; recruit; recurrent neural network; relating to nervous system; response; sensory integration; social anxiety

Summary An animal’s innate behavior responses to aversive stimuli involves multisensory integration of sensory information to guide the decision-making process. The long-term goal is to deepen our fundamental knowledge of the neural mechanisms underlying sensorimotor integration that underlies threat-induced defensive behavior. We will first focus on functional role of an innate tri-synaptic, long-range recurrent neural network (RNN) linking emotional regions with somatic motor cortex. Several forebrain regions, including the thalamus, amygdala and frontal cortical regions, is involved in expression of fear-related behaviors and memories. Understanding how these three regions interact is critical to deciphering the basic mechanisms of fear-triggered behavior. Recently, we discovered that a long-range RNN, which is formed by a self-feedback connectivity in the mPFC (Hidden Unit, HU), integrates inputs from upstream emotional regions (Input Unit, IU, which includes basal lateral amygdala, insular cortex) and further innervates motor cortex projecting neurons (Output Unit, OU). RNN is a network with self-feedback (closed-loop) connections. Recurrent circuits are capable of amplification, pattern completion and memory. The central hypothesis to be examined is that the innate long-range RNN, which is composed of: fear related emotional centers located in the basal lateral amygdala (BLA) and insular cortex (IC, i.e., a threat detection unit), decision making hidden unit in mPFC (i.e., a fear integration unit), and a downstream action initiation center located in the somatic motor cortex (sMO, i.e., a fear output unit), plays a key role in fear induced sensorimotor integration underlying defensive behavior. Understanding neuronal dynamics in the three key nodes of the RNN during innate defensive behavior, is crucial for deciphering the role of the RNN in threat- avoidance behavior selections. A specific aim with two comprehensive sub-aims are proposed to test this hypothesis: Aim 1. To determine if the RNN circuits are involved in innate defensive behavior. This aim will test the central hypothesis by: Sub-aim 1a. Examining the neuronal activity dynamics and temporal relationships in the Input Unit (IU, i.e. BLA), the hidden unit (HU, i.e. mPFC) and Output Unit (OU, i.e. sMO) during defensive avoidance behavior. Sub-aim 1b. Testing the sufficiency and necessity of activation of the key node of the RNN, HU and the final output node of the RNN: sMOs, in mediating defensive avoidance behavior. Successful execution of this exploratory proposal will help us obtain proof-of-concept data that will enable the pursuit of a full-scale project aimed at understanding the key role of mPFC in sensorimotor integration, and in particular the role of RNNs as fundamental computation units in emotion-related decision making.

概括 动物对厌恶刺激的天生行为反应涉及感觉的多感觉整合 指导决策过程的信息。长期目标是加深我们的基本知识 构成威胁引起的防御行为的基础的感觉运动整合的神经机制。 我们将首先关注先天三突触的远程复发性神经网络（RNN）的功能作用 带有体细胞皮层的情绪区域。几个前脑区域，包括丘脑，杏仁核和 额叶皮质区域参与与恐惧相关的行为和记忆的表达。了解如何 这三个区域相互作用对于破译恐惧触发行为的基本机制至关重要。最近， 我们发现，由MPFC中的自反射连接形成的远程RNN（隐藏） 单位，hu），来自上游情绪区域的集成输入（输入单元，IU），其中包括基本的侧面 杏仁核，岛状皮质），并进一步支配了运动皮层投射神经元（输出单元，OU）。 RNN是一个 具有自馈（闭环）连接的网络。复发电路能够放大，图案 完成和内存。要研究的中心假设是先天的远程RNN，即 由：恐惧相关的情感中心组成 即威胁检测单元），MPFC中的决策隐藏单位（即恐惧整合单元）和下游 动作启动中心位于躯体运动皮层（SMO，即恐惧输出单元）中，在恐惧中起关键作用 诱发防御行为的诱导感觉运动积分。了解这三个动力学 在先天防御行为期间，RNN的关键节点对于破译RNN在威胁中的作用至关重要 - 避免行为选择。提出了一个具有两个全面子iams的特定目标来测试这一点 假设：目的1。确定RNN电路是否参与先天防御行为。这个目标将测试 中央假设由：子-AIM 1A。检查神经元活动动态和临时关系 在防御性期间，输入单元（IU，即BLA），隐藏单元（HU，MPFC）和输出单元（OU，SMO） 回避行为。 Sub-aim 1B。测试RNN关键节点的安全性和必要激活， HU和RNN：SMOS的最终输出节点在介导防御避免行为中。成功的 执行此探索性建议将有助于我们获得概念证明数据，以实现追求 全面项目旨在了解MPFC在感觉运动集成中的关键作用，尤其是 RNN作为基本计算单元在与情绪相关的决策中的作用。