Neurogenetic Control of Amygdala Functions

杏仁核是表达恐惧和焦虑行为的关键大脑区域。许多影响恐惧和焦虑的受体(如大麻素和CCK受体)表达在新近发现的杏仁核基底外侧抑制神经元上。我们建议使用新的遗传方法来控制两种类型的抑制性神经元(那些表达惊恐诱导神经肽CCK或钙结合蛋白小白蛋白的神经元)。这些方法使用一种名为腺相关病毒的病毒，将特殊设计的M受体基因导入小鼠杏仁核神经元。一旦这些受体在CCK或小白蛋白GABA神经元上表达，这些神经元就可以被全身给药兴奋或抑制。这些方法旨在了解基因定义的神经元和受体是如何控制情绪的，特别是在行为上测量的恐惧和焦虑。我们将使用惊吓反射、高架迷宫、空地运动和条件性恐惧任务来测试这些基因激活或基因抑制的小鼠。然后，我们将研究这些小鼠对杏仁核内影响惊吓、恐惧和焦虑的治疗的反应，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.