Network dynamics of vHip-amygdala-mPFC circuit in innate and learned anxiety

先天性和习得性焦虑中 vHip-amygdala-mPFC 回路的网络动力学

基本信息

批准号：
8015593
负责人：
Ekaterina Likhtik
金额：
$ 3.72万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-12 至 2011-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Anxiety disorders include a broad repertoire of behaviors with differing etiologies. For instance, generalized anxiety disorder (GAD) is a state of innate and chronic fear, whereas post-traumatic stress disorder (PTSD) is an anxious response to learned fear that is acquired and cue dependent. The main goal of this proposal is to identify the differing ways in which implicated brain regions process these two types of anxiety. Research has identified the basolateral complex of the amygdala (BLA), the medial prefrontal cortex (mPFC) and the ventral portion of the hippocampus (vHip) as important for various aspects of anxiety processing. The proposed work will dissociate the behavior-driven dynamics of the network formed by these three areas during learned versus innate anxiety. The vHip, BLA and mPFC are directly connected, suggesting that they form a network, the interactions of which could constitute the basis for learned and chronic anxiety phenotypes. Indeed, the vHip and BLA have convergent inputs to the mPFC, which has been suggested as a means of integrating anxiety and context information in the cortex. Separate studies have demonstrated that in innate anxiety paradigms, the vHip and mPFC increase their communication, whereas conditioned fear increases synchrony between the hippocampus and BLA. In contrast, the mPFC and amygdala are thought to act in concert during extinction of learned fear. However, data is lacking on how the mPFC, BLA and vHip integrate or differentiate innate versus learned anxiety. Therefore, we aim to study the network dynamics of this circuit using chronic multisite recordings in vivo in conjunction with behavioral assays probing both types of anxiety. We will test the hypothesis that there are dissociable levels of cooperation between the vHip, BLA and mPFC as a function of the anxiety provoking scenario that is experienced. In addition, behavior and electrophysiological recordings will be used to test the idea that disruption of 5HT1A receptor signaling, an established model of hippocampal dependent anxiety, will enhance innate anxiety via increased vHip-mPFC coupling, while leaving intact amygdala-hippocampal signaling as well as learned anxiety. Given the prevalence of anxiety disorders in the United States and worldwide, as well as their high mortality and high cost to society, the translational nature of this proposal is undoubtedly beneficial to public heath. In particular, by examining the changing ways in which the ventral hippocampus, amygdala and medial prefrontal cortex interact during different anxiogenic scenarios, we aim to provide a network-level approach for differentiating between learned and innate anxiety in humans. The ultimate goal of this work is to create a framework for etiology-tailored therapies of anxiety.

描述（由申请人提供）：焦虑症包括广泛的病因行为行为。例如，普遍的焦虑症（GAD）是一种先天和慢性恐惧的状态，而创伤后应激障碍（PTSD）是对获得的恐惧的焦虑反应，并依赖于提示。该提案的主要目标是确定与大脑区域有关这两种焦虑的不同方式。研究确定了杏仁核（BLA），内侧前额叶皮层（MPFC）和海马腹侧部分（VHIP）的基底外侧复合物对焦虑处理的各个方面都很重要。所提出的工作将解离这三个领域在学识渊博的与先天焦虑期间形成的网络的行为驱动动力学。 VHIP，BLA和MPFC是直接连接的，表明它们形成了一个网络，其相互作用可能构成学习和慢性焦虑表型的基础。实际上，VHIP和BLA对MPFC具有收敛的输入，该输入被认为是在皮层中整合焦虑和上下文信息的一种手段。单独的研究表明，在天生的焦虑范式中，VHIP和MPFC增加了他们的沟通，而条件的恐惧会增加海马和BLA之间的同步。相比之下，MPFC和杏仁核被认为在灭绝的恐惧时会共同起作用。但是，缺乏关于MPFC，BLA和VHIP如何整合或区分先天性与学习焦虑的数据。因此，我们旨在使用体内的慢性多站点记录以及探测两种类型的焦虑的行为分析，研究该电路的网络动力学。我们将检验以下假设：VHIP，BLA和MPFC之间存在可分离的合作水平，这是焦虑引起的情况的函数。此外，将使用行为和电生理记录来测试以下想法：5HT1A受体信号的破坏是海马依赖焦虑的既定模型，将通过增加Intact Amygdala-Hippocampal信号传递以及学习的焦虑来增强先天性焦虑。鉴于美国和全世界的焦虑症患病率，以及他们对社会的高死亡率和高昂的成本，该提议的转化性质无疑对公共荒地有益。特别是，通过检查腹侧海马，杏仁核和内侧前额叶皮质在不同的焦虑症情况下相互作用的不断变化的方式，我们旨在提供一种网络级别的方法，以区分人类学习和先天的焦虑。这项工作的最终目标是为焦虑的病因学疗法创建一个框架。