Spacial and temporal role of the 5-HT1AR in anxiety

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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.