Spacial and temporal role of the 5-HT1AR in anxiety

描述（由申请人提供）：本提案旨在研究5-HT 1A受体在调节焦虑中的作用。我们的目标是确定大脑区域和发育时间点，在此期间，5-HT 1A受体建立正常或“野生型”（WT）的焦虑水平的动物的一生。提出的研究源于我们的研究结果，使用诱导型5-HTIA救援（1AR）小鼠，有条件地表达5-HTIA受体仅在某些突触后位点。我们的研究结果表明，突触后5-HT 1A受体的表达是需要出生后第5和21天之间的某个时候，小鼠表现出WT，而不是5-HT 1A敲除（1AKO）（增加）的焦虑水平在成年期。我们将结合使用分子生物学和行为学工具来验证我们的假设。我们建议进一步对现有的1AR小鼠进行行为学表征，以更严格地定义5-HT 1A受体建立WT焦虑水平的关键时间。我们还建议使用细菌人工染色体（BAC）策略生成多个新的1AR系，以更精确地剖析由5-HTIA受体建立的对焦虑水平的持久影响发生的时间和地点。

DESCRIPTION (provided by applicant): This proposal aims to examine the role of 5-HT1A receptor in modulating anxiety. We aim to determine the brain region and developmental time point during which 5-HT1A receptors establish normal or "wild-type" (WT) anxiety levels for the lifetime of the animal. The proposed studies stem from our findings using inducible 5-HTIA rescue (1AR) mice, which conditionally express 5-HTIA receptors only in certain postsynaptic sites. Our findings suggest that the expression of postsynaptic 5-HT1A receptors is required sometime between postnatal days 5 and 21 for mice to exhibit WT rather than 5-HT1A knockout (1AKO) (increased) anxiety levels in adulthood. We will use a combination of molecular biological and behavioral tools to test our hypotheses. We propose to further behaviorally characterize the existing 1AR mice to more narrowly define the critical time for the 5-HT1A receptor to establish WT anxiety levels. We also propose to generate multiple novel 1AR lines using the bacterial artificial chromosome (BAC) strategy to dissect more precisely where and when the lasting effect on anxiety levels, established by the 5-HTIA receptor, takes place.