Neural circuits regulating flight and panic behavior.

调节飞行和恐慌行为的神经回路。

基本信息

批准号：
10765755
负责人：
Jonathan P Fadok
金额：
$ 7.61万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10765755
关键词：
Alprazolam Amygdaloid structure Anxiety Behavior Behavior Control Behavioral Behavioral Paradigm Brain Calcium Carbon Dioxide Cells Characteristics Complex Corticotropin-Releasing Hormone Data Development Disease Emotional Foundations Freezing Fright Glutamates Goals Hippocampus Hypothalamic structure Image Knowledge Mediating Mental disorders Mission Modeling Monitor Mus Neurobiology Neurons Neurosciences Output Panic Panic Disorder Pathway interactions Pattern Perception Population Population Projection Positioning Attribute Post-Traumatic Stress Disorders Prevention Psychological Theory Public Health Regulation Research Role Source Specific Phobia Stimulus Structure Substance Use Disorder System Testing Therapeutic Trauma United States National Institutes of Health Viral Vector Xanax addiction comorbidity delivery vehicle design disability emotional behavior extracellular in vivo innovation midbrain central gray substance neural neural circuit neural correlate neuromechanism neuronal circuitry novel novel strategies optogenetics post-traumatic stress response theories

项目摘要

PROJECT SUMMARY Emotional behaviors, such as defensive responses to threat, are often dysregulated in mental illness. Currently, there is a poor understanding of the neural mechanisms that control transitions between modes and magnitudes of defensive responding. Obtaining such knowledge will provide significant progress toward the long-term goal of providing foundational knowledge used for the development of better therapeutics for mental illness. The overall objective of this application is to identify how distributed neuronal circuits control transitions to active forms of defensive behav- ior. The central hypothesis is that a widespread brain network that includes the central amygdala (CEA), ventromedial hypothalamus (VMH), periaqueductal grey (PAG), insular cortex (IC), and ventral hippocampus (vHIPP) controls defensive response transitions. The rationale that under- lies this proposal is that an enhanced understanding of these complex behavioral states and cir- cuits will provide foundational data for understanding multiple psychiatric disorders and their comorbidity. The proposed research tests the central hypothesis with three specific aims: 1) Iden- tify the functional role of specific projection pathways in defensive action selection; 2) Determine the impact of structures afferent to the CEA on flight behavior; and 3) Define the neuronal activity patterns that encode shifts in defensive states from freezing to flight to panic. The first aim will use viral vector delivery strategies and optogenetics to target and manipulate specific output path- ways of the CEA. The second aim will use retrograde targeting strategies to manipulate afferents to the CEA. Finally, the third aim will use deep-brain calcium imaging to monitor neural activity patterns in specific populations of projection neurons while mice transition through escalating lev- els of defensive responding. Successful completion of the proposed research will define mecha- nisms by which widespread brain networks mediate switching to active modes of defensive be- havior. The proposed research is innovative because it substantially departs from the status quo by investigating how the brain coordinates transitions between defensive behaviors. This will be significant because it will lay a foundation that facilitates understanding of the neuronal circuit basis of the maladaptive responses associated with mental illness. Indeed, this novel systems neuroscience approach to understanding how fear states are encoded will open new avenues of research into the neurobiological underpinnings of anxiety- and trauma-related mental health dis- orders, such as posttraumatic stress and panic disorder.

项目概要情绪行为，例如对威胁的防御反应，通常在心理上失调。疾病。目前，人们对控制转换的神经机制还知之甚少。防御反应的模式和程度之间。获得此类知识将提供在提供用于以下方面的基础知识的长期目标方面取得了重大进展开发更好的精神疾病治疗方法。该应用程序的总体目标是确定分布式神经元回路如何控制向主动形式的防御行为的转变或。核心假设是，包括中央杏仁核在内的广泛大脑网络 (CEA)、下丘脑腹内侧 (VMH)、导水管周围灰质 (PAG)、岛叶皮质 (IC) 和腹侧海马（vHIPP）控制防御反应转换。理由如下—— 这个提议的谎言是增强对这些复杂的行为状态和环境的理解 cuits 将为理解多种精神疾病及其症状提供基础数据合并症。拟议的研究测试了具有三个具体目标的中心假设：1）Iden- 明确特定投射路径在防御行动选择中的功能作用； 2）确定传入 CEA 的结构对飞行行为的影响； 3) 定义神经元活动编码防御状态从冻结到逃跑再到恐慌的转变的模式。第一个目标将使用病毒载体传递策略和光遗传学来瞄准和操纵特定的输出路径- CEA 的方法。第二个目标将使用逆行靶向策略来操纵传入给 CEA。最后，第三个目标将使用深部脑钙成像来监测神经活动当小鼠通过逐步升级的水平过渡时，特定投射神经元群体的模式防御性回应的 els。成功完成拟议的研究将定义机械- 广泛的大脑网络通过这种机制介导向主动防御模式的转变行为。拟议的研究具有创新性，因为它大大偏离了现状通过研究大脑如何协调防御行为之间的转换。这将是意义重大，因为它将为促进理解神经元回路奠定基础与精神疾病相关的适应不良反应的基础。事实上，这个新颖的系统理解恐惧状态如何编码的神经科学方法将为研究焦虑和创伤相关心理健康问题的神经生物学基础命令，例如创伤后应激障碍和恐慌症。