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 动物对厌恶刺激的先天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础知识。 感觉运动整合的神经机制是威胁引起的防御行为的基础。 我们将首先关注先天三突触、远程循环神经网络 (RNN) 连接的功能作用 情绪区域与躯体运动皮层的几个前脑区域，包括丘脑、杏仁核和 额叶皮质区域参与恐惧相关行为和记忆的表达。 这三个区域的相互作用对于破译恐惧引发行为的基本机制至关重要。 我们发现了一个远程 RNN，它是由 mPFC（隐藏层）中的自反馈连接形成的 Unit，HU），整合来自上游情感区域的输入（Input Unit，IU，其中包括基础侧向情感区域） 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，RNN）。 具有自反馈（闭环）连接的网络能够放大、模式。 要检验的中心假设是先天的长程 RNN，即 组成：位于基底外侧杏仁核（BLA）和岛叶皮质（IC， 即威胁检测单元）、mPFC 中的决策隐藏单元（即恐惧整合单元）和下游 位于躯体运动皮层的动作启动中心（sMO，即恐惧输出单元），在恐惧中起着关键作用 诱导防御行为背后的感觉运动整合。了解三者的神经动力学。 RNN 在先天防御行为期间的关键节点对于破译 RNN 在威胁中的作用至关重要 提出了一个带有两个综合子目标的特定目标来测试这一点。 假设：目标 1. 确定 RNN 电路是否参与先天防御行为。该目标将进行测试。 中心假设：子目标 1a 检查神经活动动态和时间关系。 防御时的输入单元（IU，即 BLA）、隐藏单元（HU，即 mPFC）和输出单元（OU，即 sMO） 子目标 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：sMOs，成功调解防御性回避行为。 执行这一探索性提案将有助于我们获得概念验证数据，从而实现 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 作为基本计算单元在情感相关决策中的作用。