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: 10626968
• 负责人: Qian-Quan Sun
• 金额: $ 18.06万
• 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 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10626968
• 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; frontal lobe; member; multisensory; neural; neuromechanism; novel; post-traumatic stress; recruit; recurrent neural network; 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.

总结 动物对厌恶性刺激的先天行为反应涉及感觉的多感觉整合， 信息来指导决策过程。长期目标是加深我们的基础知识 感觉运动整合的神经机制是威胁诱导的防御行为的基础。 我们将首先关注先天三突触，长程递归神经网络（RNN）连接的功能作用 情感区域和躯体运动皮层几个前脑区域，包括丘脑，杏仁核和 额叶皮层区域，参与表达与恐惧相关的行为和记忆。了解如何 这三个区域的相互作用对于解释恐惧引发行为的基本机制至关重要。最近， 我们发现，一个远程RNN，这是由一个自反馈连接在mPFC（隐藏）形成的 单位，HU），整合来自上游情绪区域的输入（输入单位，IU，包括基底外侧 杏仁核，岛叶皮层），并进一步支配运动皮层投射神经元（输出单元，OMT）。RNN是一个 自反馈（闭环）连接网络。循环回路能够放大， 完成和记忆。要检验的中心假设是先天的长距离RNN， 包括：位于基底外侧杏仁核（BLA）和岛叶皮层（IC， 也就是说，威胁检测单元），mPFC中的决策隐藏单元（即，一个恐惧整合单元），和一个下游 位于躯体运动皮层（sMO，即，恐惧输出单元），在恐惧中起着关键作用 诱导防御行为下的感觉运动整合。了解三个神经元的动力学 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- 回避行为选择提出了一个具体目标和两个综合子目标来检验这一点 假设：目标1。以确定RNN回路是否参与先天防御行为。这一目标将检验 核心假设：子目标1a。检查神经元活动动力学和时间关系， 在防御期间，输入单元（IU，即BLA）、隐藏单元（HU，即mPFC）和输出单元（HU，即sMO 回避行为次级目标1b.测试RNN关键节点激活的充分性和必要性， HU和RNN的最终输出节点：sMO，在介导防御性回避行为中。成功 这一探索性建议的执行将有助于我们获得概念验证数据，从而实现 一个全面的项目，旨在了解mPFC在感觉运动整合中的关键作用，特别是 RNN在情感相关决策中作为基本计算单元的作用。