Variance in sibling mothering received and adult mothering, anxiety and serotonin

描述(由申请人提供)：接受兄弟姐妹抚养的差异和成年母亲的差异、焦虑和5-羟色胺这项NRSA提案的长期目标是确定兄弟姐妹在母亲护理方面的差异如何影响与后来的兄弟姐妹差异有关的机制：1)母亲行为，2)焦虑样行为，3)5-羟色胺合成 然后释放。这项研究是新颖而重要的，因为在人类和非人类动物中，众所周知，不同家庭之间获得的产妇护理差异很大，并对后代的神经和社会发育产生巨大影响，但在家庭内考察这一现象的研究很少。使用老鼠模型，我将研究出生后早期母婴互动与成年育儿、焦虑相关行为和姐妹间5-羟色胺活动之间的关联。在具体目标1中，我将对生命的前十天接受的母爱进行详细的观察，并确定与低舔的姐妹相比，高舔的雌性是否为自己的后代提供更多的母爱。在成年期间，这些雌性老鼠还将在高架加迷宫(一种经过充分验证的啮齿动物类焦虑行为的衡量标准)上进行测试，以确定焦虑程度的差异是否与它们在育儿方面的差异有关。在特定的目标2中，我将使用Western blots来测量中缝背侧色氨酸羟基酶2(TPH2，负责脑5-羟色胺合成的主要酶)的表达，假设与其低舔姐妹相比，高舔雌性中缝中缝中的色氨酸羟化酶2表达上调。最后，在特定的目标3中，我将确定终纹腹侧床核(BSTv)中的5-羟色胺释放是否高于它们的低舔姐妹。终纹腹床核是从DR接受密集的5-羟色胺投射的区域，与母亲的行为和焦虑有关。为了做到这一点，我将使用体内微透析来测量产后姐妹与幼崽互动时BSTv中5-羟色胺的释放。在这一目标的第二个实验中，我将确定是否可以通过给低舔的姐妹服用5-HT1a受体激动剂flesinoxan来最大限度地减少姐妹间的育儿差异。在这项建议中，我的目标是澄清围产期焦虑相关行为和母亲行为的个体差异的早期预测因素，这将促进对导致女性患成人焦虑症风险的发展轨迹的更好理解。

DESCRIPTION (provided by applicant): Variance in sibling mothering received and adult mothering, anxiety and serotonin The long-term objectives of this NRSA proposal are to identify how variance among siblings in maternal care received influences mechanisms related to later sibling differences in: 1) maternal behavior, 2) anxiety-like behaviors, and 3) serotonin synthesis and release. This research is novel and important because in humans and non-human animals, it is well-known that variance in maternal care received greatly differs between families and has tremendous effects on offspring neurological and social development, yet studies examining this phenomenon within families are scarce. Using a rat model, I will examine the association between mother- infant interactions during the early postnatal period and adult mothering, anxiety-related behaviors, and serotonin activity among sisters. In Specific Aim 1, I will conducted finely detailed observations of maternal care received during the first ten days of life and determine if high-licked females provide more maternal care to their own offspring compared to their low-licked sisters. During adulthood, these females will also be tested on the elevated plus maze (a well-validated measure of anxiety-like behavior in rodents) to determine if differences in anxiety are associated with their differences in mothering. In Specific Aim 2, I wil use Western Blots to measure expression of tryptophan hydroxylase 2 (TPH2, the major enzyme responsible for brain serotonin synthesis) in the dorsal raphe with the hypothesis that it is upregulated in high-licked females compared to their low-licked sisters. Finally, in Specific Aim 3, I will determine if serotonin release in the ventral bed nucleus of the stria terminalis (BSTv), an area receiving dense serotonergic projections from the DR and associated with maternal behavior and anxiety, is higher in high-licked females than their low-licked sisters. To accomplish this, I will use in vivo microdialysis to measure serotonin release in the BSTv in postpartum sisters while they interact with pups. In a second experiment in this Aim, I will determine if variability among sisters in mothering can be minimized by administration of the 5-HT1a receptor agonist, flesinoxan, to low-licked sisters. In this proposal, I aim to clarify early perinatal predictors of individual differences in anxiety-related and mothering behaviors, which will promote a better understanding of developmental trajectories leading women toward risk for adult anxiety disorders.