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

攻击性是一种广泛的自然发生的行为，具有一系列适应功能，包括获得配偶和资源。性腺产生的睾丸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，在睾丸激素水平检测不到的非繁殖季节，攻击性可能既强烈又普遍。这意味着攻击性受到不止一种机制的调控，人们对非繁殖型攻击性是如何调控的知之甚少。本研究以雌性西伯利亚仓鼠为模型，试图了解攻击性季节性变化背后的生理机制。这项工作是高度综合性的，不同于大多数其他考察单一因素的研究，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发挥作用来控制女性的季节性攻击性。这些研究将为调节攻击性和更广泛的社会行为的生理机制提供重要的见解。此外，这项提议将允许继续指导本科生和高中生从事与这项工作直接相关的研究。这些研究成果的传播将包括公开讲座、科学会议、期刊文章，以及专门的地区性研讨会和组织，重点关注科学界未被充分代表的少数群体的进步。研究人员迄今的数据表明，褪黑素是编码光周期的荷尔蒙信号，推动攻击性的季节性变化，此外，肾上腺激素，如DHEA，而不是性激素，可能通过在动物不繁殖期间转化为活跃的雄激素或雌激素来间接调节攻击性。为了研究荷尔蒙从性腺到肾上腺来源的季节性转换，拟议的研究测试了DHEA介导非繁殖季节攻击和褪黑素调节DHEA释放及其转化为活性荷尔蒙的假设，后者随后可以作用于神经受体。具体目标1将通过免疫细胞化学将攻击性和季节性褪黑素的季节性变化与神经受体谱(雄激素和雌激素受体)以及转换酶(芳香酶，将T转化为雌二醇的酶)联系起来。具体目标2将通过用ACTH挑战不同光周期的动物，并评估DHEA的释放，来确定DHEA水平的变化是否预测不同季节个体的攻击性。最后，特殊目标3将通过将肾上腺与其他负责DHEA释放的器官分离，并使用体外生物测定来解决褪黑素对该器官的局部作用及其随后产生的DHEA，来检验这样的假设，即褪黑素的短日增加介导了DHEA的季节性变化。总的来说，这项拟议的工作采取了整体生物体的方法，并研究了荷尔蒙对多种组织的直接作用，以确定雌性仓鼠季节性攻击性的机制，使用多层次的分析。为了方便数据的适当存储和访问，手稿将在可能的情况下以开放获取的格式发布，并在实验室网站上发布。演讲将在国际和国家会议上进行，以及在当地场地向包括高中在内的非专业观众发表。在对主要项目的样品进行处理后，样品将被存档，供感兴趣的各方进行合作。最后，PI将与印第安纳大学信息技术服务部门合作，将研究数据综合体(RDC)上的数据存档，RDC是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.