Genetic tools and imaging technology for mapping cholinergic engrams of anxiety

 描述（由申请人提供）：该申请将开发新的遗传工具，并推进当前的程序，以精确和快速地绘制行为特异性记忆痕迹。拟议的研究还将提供独特的洞察胆碱能信号在整合网络中的作用，焦虑行为的基础。微调电路活动的调节性递质是神经编码的重要组成部分，尽管有些神秘。也许最不了解-但最广泛分布-在中枢神经系统的神经调质是乙酰胆碱（ACh）。我们建议推进两个方面的遗传活性映射，以跟踪胆碱能信号在多大程度上参与了回忆的焦虑激发的经验，在小鼠。基底前脑胆碱能神经元在回忆焦虑诱导的行为过程中显示阈上激活，被定义为登记在记忆印迹中（Eng+）。将通过遗传标记激活的胆碱能神经元及其从基底前脑到扣带和前额叶皮质以及海马和杏仁核区域的投射来映射Eng+神经元，这些区域与焦虑相关行为有关。

 DESCRIPTION (provided by applicant): This application will develop new genetic tools and advance current procedures for precise and rapid mapping of behavior specific memory engrams. The proposed studies also will provide unique insight into the role of cholinergic signaling in the integrated networks that underlie anxiety behaviors. Modulatory transmitters that fine tune circuit activity are essential, albeit somewhat cryptic, components of neural coding. Perhaps the least understood- and yet most broadly distributed- neuromodulator in the CNS is acetylcholine (ACh). We propose to advance two aspects of genetic activity-mapping to track the extent to which cholinergic signaling is engaged by recall of anxiety-provoking experience in the mouse. Basal forebrain cholinergic neurons that display suprathreshold activation during recall of anxiety-induced behaviors are defined as enrolled in the memory engram (Eng+). Eng+ neurons will be mapped by genetically tagging activated cholinergic neurons and their projections from the basal forebrain to cingulate and prefrontal cortices as well as to hippocampal and amygdala regions that are implicated in anxiety related behavior.