Genetic tools and imaging technology for mapping cholinergic engrams of anxiety

 描述(由申请人提供)：这项申请将开发新的遗传工具，并推进当前的程序，以准确和快速地绘制行为特定的记忆印记。这项拟议的研究还将为胆碱能信号在构成焦虑行为的整合网络中的作用提供独特的见解。微调电路活动的调制发射器是神经编码的基本组成部分，尽管有些隐晦。也许在中枢神经系统中了解最少，但分布最广的神经调节剂是乙酰胆碱(ACh)。我们建议推进遗传活动图谱的两个方面，以跟踪胆碱能信号通过回忆小鼠引发焦虑的经历而参与的程度。在焦虑诱导的行为回忆过程中表现出阈值以上激活的基底前脑胆碱能神经元被定义为登记在记忆印记(Eng)中。通过基因标记激活的胆碱能神经元及其从基底前脑到扣带回和前额叶皮质以及与焦虑相关行为有关的海马区和杏仁体的投射，将绘制ENG神经元的图谱。

 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.