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 防御性行动。越来越多的证据表明，杏仁核能很好地整合信息。 关于威胁的信息，并引导或改变一系列潜在防御行为的反应。在这两个地方 在人类和小鼠身上，杏仁核在对窒息威胁的防御反应中起着至关重要的作用， 以体内系统性二氧化碳(CO2)水平上升为信号。损毁杏仁核，或操纵它 更准确地说，在其他方面，减少了吸入二氧化碳引起的一些防御行为(例如，冻结) 同时增加其他人(例如，战斗或逃跑)。因为吸入二氧化碳会引起各种 以强健、可重现和浓度依赖的方式进行防御响应，二氧化碳提供了 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……里面 在这一应用中，我们建议使用最先进的神经元来研究二氧化碳诱发的防御行为。 特定操作和电生理记录解构特定神经元群体在脑内的作用 杏仁基底外侧核(BLA)。我们假设不同的防御行为受到不同的调控 通过BLA，BLA中的主神经元和中间神经元各自扮演着独特的角色。为了测试这一点 假设我们将使用遗传、光遗传和电生理方法来特别激活和 使特定的BLA神经元群体沉默，并量化其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是如何调节不同的防御行为的。 了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。这一知识将会 最终影响防御行为不适当极端的精神疾病，如恐慌 精神障碍和创伤后应激障碍。

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.