Neurogenetic Control of Amygdala Functions

杏仁核是大脑中表达恐惧和焦虑行为的关键区域。许多影响恐惧和焦虑的受体（如大麻素和CCK受体）在最近发现的基底外侧杏仁核抑制性神经元上表达。我们建议用新的遗传方法研究两种类型的抑制性神经元（表达恐慌诱导神经肽CCK或钙结合蛋白Parvalbumin）来控制这些神经元。这些方法使用一种称为腺相关病毒的病毒，将特别设计的毒蕈碱受体基因传递到小鼠的杏仁核神经元中。一旦这些受体在CCK或小白蛋白GABA神经元上表达，神经元可以被系统给予的药物激活或抑制。这些方法旨在了解基因定义的神经元和受体如何控制情绪，特别是恐惧和焦虑的行为测量。我们将测试这些基因激活或基因抑制的小鼠使用惊吓反射，升高加上迷宫，露天运动和条件恐惧任务。然后，我们将研究这些小鼠对影响惊吓、恐惧和焦虑的杏仁核内治疗的反应，以确定这些神经元对催产素、大麻素或CCK受体阻滞剂的敏感性有多大影响。

The amygdala is a key brain region for the behavioral expression of fear and anxiety. Many receptors that influence fear and anxiety (such as cannabinoid and CCK receptors) are expressed on basolateral amygdala inhibitory neurons that have been recently identified. We propose to study two types of inhibitory neurons (those expressing the panic-inducing neuropeptide CCK or the calcium-binding protein Parvalbumin) using new genetic methods to control these neurons. These methods use a virus, called adeno-associated virus, to pass specially designed muscarinic receptor genes into mouse amygdala neurons. Once these receptors are expressed on CCK or Parvalbumin GABA neurons, the neurons can be excited or inhibited by a drug administered systemically. These methods are designed to understand how genetically defined neurons and receptors control emotions, in particular fear and anxiety measured behaviorally. We will test these genetically-activated or genetically-inhibited mice using startle reflex, elevated plus maze, open-field locomotion and conditioned fear tasks. Then we will study how these mice respond to intra-amygdala treatments that affect startle, fear and anxiety, to determine how much these neurons influence sensitivity to oxytocin, cannabinoids or CCK receptor blockers.