CAREER: Signal to Noise: How Complex Social Information Regulates Brain Genomics and Behavior

生活经历通过环境输入和大脑中的基因活动之间的复杂相互作用来改变个人行为；目前尚不清楚为什么某些经历对行为有持久的影响，而其他影响很容易逆转。这个问题与动物生物多样性有关，但也与人类健康研究有关，人类健康研究的一个目标是减轻社会创伤等经历对行为的影响。虽然动态的大脑基因活动是经验引起的行为变化的基础，但调节经验持续性的确切机制尚不清楚。例如，经验可能会在化学上改变大脑DNA，从而永久性地改变基因活动。然而，基因活动本身的变化可能是暂时的，但会导致其他影响行为的因素发生永久性变化，比如大脑结构。这项研究使用基因调控机制的实验操作来确定某些机制是否可靠地预测了一种经历的寿命。这些研究的对象是蜜蜂(蜜蜂)，一种关键的作物传粉者，在社会经验、大脑基因活动和攻击行为之间建立了良好的关系。由学生和养蜂人组成的团队将完成研究目标，并组织一次峰会，向高中生介绍农业STEM的研究成果和学术、行业和非营利性职业机会。除了填补行为多样性研究中的关键知识空白外，该项目还将提高公众科学素养，并加强学术界内外学生和专业人士之间的伙伴关系。这些步骤有助于提高STEM劳动力的多样性、保留率和职业成功的总体结果。在蜜蜂中，成年蜜蜂的防御攻击性和大脑基因表达会随着几天过程中积累的社会信息而持续变化。在某种程度上，这些表型还对有关蜂箱受到威胁的即时信息做出反应，使研究人员能够评估持续的社会体验被新信息更新的情况。持久的影响与大脑DNA甲基化的变化和周围内分泌组织中脂肪含量的减少有关，这种组织已知会影响大脑基因的表达，即脂肪体。因此，社会经验的长寿可能是大脑DNA甲基化、内分泌信号模式或两者兼而有之的基因调控影响的结果。研究人员使用错综复杂的成年社交操作来培育出表现出类似攻击性水平的蜜蜂，但具有不同的基因调控基础(大脑DNA甲基化、脂肪体内脂肪含量的变化，或两者都有)。这些蜜蜂将被用来检验在行为、脑生理(线粒体生物能量学)和基因组功能(使用RNA-SEQ、亚硫酸氢盐-SEQ和ATAC-SEQ测量的基因表达和染色质可及性)方面，哪些调控机制可以预测对新信息的反应强度。幼蜂也表现出其成虫前环境的持续行为影响。对幼虫的操纵和对成虫行为的测量将被用来确定在成虫中发现的长寿机制是否也适用于第二生命阶段。这项研究解决了大脑基因组学和行为可塑性之间的关键知识差距，包括外围系统和大脑表观遗传机制如何协同工作来调节大脑基因的表达和行为。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Life experiences change individual behavior through complex interactions between environmental inputs and gene activity in the brain; it is unclear why certain experiences have lasting effects on behavior while other effects are easily reversed. This question is relevant to animal biodiversity, but also human health research, where one goal is to mitigate the behavioral impacts of experiences like social trauma. Though dynamic brain gene activity underlies experience-induced changes in behavior, the exact mechanisms that regulate the persistence of an experience are unclear. For example, experience may chemically alter brain DNA and therefore permanently change gene activity. However, a change in gene activity itself may be temporary, but lead to permanent changes in other factors that influence behavior, like brain structure. This study uses experimental manipulations of gene regulating mechanisms to determine whether certain ones reliably predict the longevity of an experience. The subject of these studies is the honey bee (Apis mellifera), a critical crop pollinator with a well-established relationship between social experience, brain gene activity, and aggressive behavior. Teams composed of students and beekeepers will complete research objectives and organize a summit that introduces high school students to research results and academic, industry, and non-profit career opportunities in Agricultural STEM. In addition to filling critical knowledge gaps in the study of behavioral diversity, this project will improve public science literacy and enhance partnerships among students and professionals inside and outside of academia. These steps contribute to an overall outcome of increased STEM workforce diversity, retention and career success.In honey bees, adult defensive aggression and brain gene expression are persistently changed by social information accrued over the course of several days. To a degree, these phenotypes are also responsive to immediate information about threats to the beehive, enabling researchers to assess the circumstances under which persistent social experiences are updated by new information. Persistent effects are correlated with changes in brain DNA methylation and decreased lipid content in a peripheral endocrine tissue known to impact brain gene expression, the fat body. Thus, the longevity of social experience could be a result of the gene regulatory impacts of brain DNA methylation, endocrine signaling patterns, or both. Researchers use intricate adult social manipulations to produce bees that display similar levels of aggression, but with different gene regulatory underpinnings (variation in brain DNA methylation, fat body lipid content, or both). These bees will be used to examine which regulatory mechanisms predict the strength of response to new information, in terms of behavior, brain physiology (mitochondrial bioenergetics), and genome function (gene expression and chromatin accessibility measured using RNA-seq, bisulfite-seq and ATAC-seq). Larval bees also show persistent behavioral effects of their pre-adult environment. Manipulations of larvae and measures of adult behavior will be used to determine whether the longevity mechanisms identified in adults also apply to a second life stage. This study addresses critical knowledge gaps in the relationship between brain genomics and behavioral plasticity, including how peripheral systems and brain epigenetic mechanisms work together to regulate brain gene expression and behavior.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.