Neural circuits regulating flight and panic behavior.

项目总结 情绪行为，如对威胁的防御性反应，通常在心理上是失调的 生病了。目前，人们对控制过渡的神经机制知之甚少 在防御反应的方式和程度之间。获得这样的知识将提供 在长期目标方面取得重大进展，即提供用于 开发更好的精神疾病治疗方法。这个应用程序的总体目标是 为了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- IOR。中心假说是包括中央杏仁核在内的广泛的大脑网络 (CEA)、下丘脑腹内侧部(VMH)、中脑导水管周围灰质(PAG)、岛叶皮质(IC)和 腹侧海马区(VHIPP)控制防御反应的转换。理由是，在- 这一建议是，加强对这些复杂的行为状态和循环的理解-- CUITS将为理解多种精神障碍及其 合并症。这项拟议的研究以三个具体目标来检验中心假设：1)IDEN- 明确特定投射通路在防御动作选择中的功能作用；2)确定 CEA传入结构对飞行行为的影响；3)确定神经元的活动 编码防御状态从冰冻到逃跑再到恐慌的模式。第一个目标是 使用病毒载体传递策略和光遗传学来靶向和操纵特定的输出路径- CEA的方式。第二个目标将使用逆行靶向策略来操纵传入 致CEA。最后，第三个目标将使用脑深部钙成像来监测神经活动 当小鼠通过水平递增的水平过渡时，特定投射神经元群体的模式 防御反应的ELS。成功完成拟议的研究将定义机械- 广泛存在的大脑网络调节向主动防御BE模式的转换。 哈沃。拟议的研究具有创新性，因为它与现状大相径庭。 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，这个新的系统 用神经科学的方法来理解恐惧状态是如何编码的，这将开辟 焦虑和创伤相关心理健康障碍的神经生物学基础研究 命令，如创伤后应激障碍和恐慌症。

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.