Basolateral amygdala circuits in defensive behavior regulation

摘要 在敌对环境中生存需要评估潜在威胁的能力，并采取最适当的措施。 防御行动。越来越多的证据表明杏仁核在整合信息方面处于有利地位 并引导或改变反应沿着一系列潜在的防御行为。无论是 对于人类和小鼠，杏仁核在对窒息威胁的防御反应中起着重要作用， 通过体内系统二氧化碳（CO2）水平升高发出信号。损害杏仁核，或者操纵它 更确切地说，在其他方面，减少了由CO2吸入引起的一些防御行为（例如冻结） 而同时增加其他的（例如战斗或逃跑）。因为吸入二氧化碳会引起各种 防御反应在一个强大的，可重复的，和浓度依赖性的方式，二氧化碳提供了一个 这是一种直接和可翻译的方法来研究杏仁核在防御行为调节中的作用。在 本申请中，我们建议使用最先进的神经元研究CO2诱发的防御行为， 特定的操作和电生理记录，以解构选择的神经元群体在 基底外侧杏仁核（BLA）。我们假设不同的防御行为受到不同的调节， BLA中的主要神经元和中间神经元各自发挥独特的作用。为了验证这一 假设我们将使用遗传学、光遗传学和电生理学方法来特异性激活和 沉默特定的BLA神经元群体，并量化对神经活动和防御行为的影响。 这些实验将使我们能够辨别这些神经元如何调节不同的防御行为。 理解引导或改变防御行为的基本机制将是至关重要的 用于识别这些过程中的异常并找到纠正它们的方法。这些知识将 最终影响心理疾病，其中防御行为是不适当的极端， 创伤后应激障碍。

Abstract Survival in a hostile environment requires the ability to assess potential threats and take the most appropriate defensive action. Accumulating evidence suggests that the amygdala is well positioned to integrate information about threats and to guide or shift responses along a spectrum of potential defensive behaviors. In both humans and mice, the amygdala plays an essential role in defensive responses to the threat of suffocation, signaled by rising systemic carbon dioxide (CO2) levels in the body. Lesioning the amygdala, or manipulating it more precisely in other ways, reduces some defensive behaviors evoked by CO2 inhalation (e.g. freezing) while simultaneously increasing others (e.g. fight-or-flight). Because CO2 inhalation evokes a variety of defensive responses in a robust, reproducible, and concentration-dependent manner, CO2 provides a straightforward and translatable approach to studying the amygdala's role in defensive behavior regulation. In this application, we propose to study defensive behaviors evoked by CO2 using state-of-the-art, neuron- specific manipulations and electrophysiological recording to deconstruct roles of select neuron populations in the basolateral amygdala (BLA). We hypothesize that distinct defensive behaviors are differentially regulated by the BLA and that principal neurons and interneurons in the BLA each play unique roles. To test this hypothesis we will use genetic, optogenetic, and electrophysiological approaches to specifically activate and silence specific BLA neuron populations and quantify the effects on neural activity and defensive behaviors. Together these experiments will allow us to discern how these neurons regulate different defensive behaviors. Understanding basic mechanisms that guide or shift defensive behaviors along their spectrum will be essential for identifying abnormalities in these processes and for finding ways to correct them. This knowledge will ultimately impact mental illnesses where defensive behaviors are inappropriately extreme such as panic disorder and post-traumatic stress disorder.