DISSERTATION RESEARCH: Neuroendocrine Mechanisms of Seasonal Aggression in Female Siberian Hamsters (Phodopus sungorus)

攻击性是一种广泛存在的自然行为，具有一系列适应性功能，包括获取配偶和资源。性腺分泌的睾丸激素通常与高水平的攻击性有关。然而，在季节性繁殖的动物中，在睾酮水平无法检测到的非繁殖季节，攻击行为可能既强烈又广泛。这意味着攻击性受到不止一种机制的调节，而对于非繁殖性攻击是如何调节的，人们知之甚少。本研究试图以雌性西伯利亚仓鼠为模型，了解其攻击性季节性变化的生理机制。这项工作是高度综合的，不像大多数其他研究只研究单一因素，它将考虑许多相关的内分泌参数及其相互作用，以了解大脑和激素如何控制女性的季节性攻击。这些研究将为更广泛地研究攻击性和社会行为的生理机制提供重要的见解。此外，该提案将允许本科生和高中生继续指导与本工作直接相关的研究。这些研究成果的传播将包括公开演讲、科学会议和期刊文章，以及专门的区域专题讨论会和组织，重点是提高科学界代表性不足的少数民族的地位。到目前为止，研究人员的数据表明，编码光周期的激素信号褪黑素驱动攻击性的季节性变化，进一步说，肾上腺激素，如脱氢表雄酮，而不是性腺激素，可能在动物不繁殖的时期通过转化为活跃的雄激素或雌激素间接调节攻击性。为了检验从性腺激素到肾上腺激素的季节性转换，提出的研究测试了以下假设：脱氢表雄酮介导非繁殖季节的攻击性，褪黑激素调节脱氢表雄酮的释放并将其转化为活性激素，然后作用于神经受体。Specific Aim 1将通过免疫细胞化学将攻击性的季节性变化和季节性褪黑激素线索与神经受体谱（雄激素和雌激素受体）以及转化酶（芳香化酶，将T转化为雌二醇的酶）联系起来。具体目标2将通过在不同的光周期用ACTH挑战动物，并评估脱氢表雄酮的释放，确定脱氢表雄酮水平的变化是否预测个体在不同季节的攻击性。最后，Specific Aim 3将通过将肾上腺从负责脱氢表雄酮释放的其他器官中分离出来，并使用体外生物测定来解决褪黑素在该器官上的局部作用及其随后产生的脱氢表雄酮，来验证褪黑素在短时间内增加介导脱氢表雄酮季节性变化的假设。总的来说，拟议的工作采取了整个有机体的方法，并通过多层次的分析来检查激素对多个组织的直接作用，以确定雌性仓鼠季节性攻击的机制。为了方便数据的适当存储和访问，稿件将尽可能以开放获取格式发布，并在实验室网站上发布。报告将在国际和国内会议上发表，也将在包括高中在内的当地场所发表。在对主要项目的样品进行处理后，将对样品进行存档，以便有关各方进行合作。最后，PI将与印第安纳大学信息技术服务部合作，将数据归档到研究数据综合体（RDC）上，这是一个托管数据库的专用服务器。

Aggression is a widespread naturally-occurring behavior serving a range of adaptive functions including access to mates and resources. Testosterone produced by the gonads is frequently associated with high levels of aggression. However, in seasonal breeding animals aggression can be both intense and widespread during the non-breeding season when testosterone levels are undetectable. This means that aggression is regulated by more than one mechanism and there is little understanding of how non-breeding aggression is regulated. This research seeks to understand the physiological mechanisms that underlie seasonal variation of aggression using female Siberian hamsters as a model. This work is highly integrative and unlike most other studies that examine single factors it will consider many relevant endocrine parameters and their interactions to understand how the brain and hormones function to control seasonal aggression in females. These studies will provide important insights into the physiological mechanisms mediating aggression, and social behavior more broadly. Additionally, this proposal will allow for the continued mentorship of undergraduates and high school students in research directly related to this work. Communication of these research findings will include public lectures and scientific conferences, and journal articles, as well as specialized regional symposia and organizations focused on the advancement of underrepresented minorities in the sciences.The researchers' data so far show that melatonin, the hormonal signal encoding photoperiod, drives seasonal changes in aggression, and further that adrenal hormones, such as DHEA, rather than gonadal hormones, may indirectly regulate aggression via conversion to active androgens or estrogens during periods when animals are non-reproductive. To examine seasonal switching from a gonadal to adrenal source of hormone, the proposed research tests the hypotheses that DHEA mediates non-breeding season aggression and that melatonin regulates DHEA release and its conversion to active hormones, which can then act on neural receptors. Specific Aim 1 will link seasonal changes in aggression and seasonal melatonin cues to neural receptor profiles (androgen and estrogen receptors) as well as a converting enzyme (aromatase, the enzyme that converts T to estradiol), via immunocytochemistry. Specific Aim 2 will determine whether changes in DHEA levels predict aggression among individuals across seasons by challenging animals in different photoperiods with ACTH, and assessing DHEA release. Lastly, Specific Aim 3 will test the hypothesis that short-day increases in melatonin mediate seasonal changes in DHEA by isolating the adrenal gland from other organs responsible for DHEA release and by using an in vitro bioassay to address localized action of melatonin on this organ and its subsequent production of DHEA. Collectively, the proposed work takes a whole organism approach and examines direct hormonal action on multiple tissues to determine the mechanisms underlying seasonal aggression in female hamsters using multiple levels of analysis. To facilitate proper storage and access of data, manuscripts will be published in open-access format, when possible, and on the lab website. Presentations will be made at international and national conferences, as well as in local venues to lay audiences, including high schools. Following processing of samples for the primary project, samples will be archived, and made accessible for collaborations from interested parties. Lastly, the PI will work with Indiana University Information Technology Services to archive data on the Research Data Complex (RDC), a dedicated server for hosting databases.