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-HT1A受体在调节焦虑中的作用。我们的目标是确定5-HT1A受体在动物一生中建立正常或“野生型”（WT）焦虑水平的大脑区域和发育时间点。我们提出的研究源于我们使用诱导性5-HTIA拯救（1AR）小鼠的发现，这些小鼠仅在某些突触后部位有条件地表达5-HTIA受体。我们的研究结果表明，小鼠在成年期表现出WT而不是5- ht1a敲除（1AKO）（增加的）焦虑水平，需要突触后5- ht1a受体在出生后5- 21天之间的某个时间表达。我们将结合使用分子生物学和行为工具来检验我们的假设。我们建议进一步对现有的1AR小鼠进行行为表征，以更严格地定义5-HT1A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，以更精确地解剖由5-HTIA受体建立的对焦虑水平的持久影响发生的地点和时间。

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.