Gene Networks Regulating Playfulness

调节游戏性的基因网络

基本信息

批准号：
10223885
负责人：
Ashley Marquardt
金额：
$ 3.84万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-26 至 2022-07-25
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10223885
关键词：
Adaptive Behaviors Adolescence Adolescent Adult Affect Aggressive behavior Amygdaloid structure Animals Attention deficit hyperactivity disorder Behavior Behavioral Bioinformatics Brain Characteristics Cognition Complex Development Exhibits Female Frequencies Future Gene Expression Gene Expression Profile Genes Genetic Transcription Housing Impairment Individual Individual Differences Mammals Masculine Maternal Behavior Medial Neurodevelopmental Disorder Neurosciences Pathway Analysis Pattern Play Prevalence Puberty Rattus Research Personnel Sampling Sex Bias Sex Differences Shapes Signal Transduction Site Social Behavior Social Development Social Interaction Sprague-Dawley Rats Territoriality Testing Time Tissues Training Viral Vector autism spectrum disorder epigenetic regulation experience experimental study functional genomics individual variation insight male neural circuit novel overexpression postnatal prevent reproductive success sex social success theories transcriptome sequencing transcriptomics

项目摘要

Project Summary Social play, or rough-and-tumble play, is a characteristic pattern of social behavior exhibited by most mammals during adolescence. While the function of play is debated, converging evidence finds it vital for appropriate social behavior, cognition, and reproductive success in adulthood. Importantly, there is a sex difference in expression of play. Males exhibit greater intensity and frequency of play than females; however, there is individual variability in that some females play at the level of high-playing males while some males play at the level of low-playing females. In a recent experiment, we aimed to use the power of these individual differences to gain novel insight into sex-dependent and sex-independent transcriptional signatures associated with play. We scored play once daily for 4 days, designating rats in the top third per sex as “high-playing” and those in the bottom third as “low- playing”, collected tissue from the medial amygdala (MeA; site of play masculinization) for RNA-sequencing (RNA-seq), and used Weighted Gene Co-Expression Network Analysis (WGCNA) to identify 22 gene co- expression modules, or networks of coordinately regulated genes. Notably, all but one of the 12 modules (for p<0.05) associated with play were sex-specific in expression, indicating a sex difference in the transcriptomic profile associated with play in males compared to females. Building on previous theories that play’s function is to shape circuitry enabling expression of adult behavior, our central hypothesis posits that the transcriptional networks in the MeA underlying expression of play are sex-specific because juvenile play regulates expression of sex-typical adult social behaviors. Using two representative sex-specific, play-associated modules, we will test this hypothesis across 3 Specific Aims (SAs). SA1 determines whether module expression causally regulates playfulness in a sex-specific manner. In this aim, we will test the effect of overexpressing module regulators from our representative sex-specific modules in the MeA and determine whether this affects play in the predicted sex only. SA2 correlates expression of juvenile play with expression of sex-typical adult social behavior, determining if individual differences in playfulness track to differences in expression of territorial aggression (males) and maternal behavior (females). Finally, SA3 determines whether module expression causally regulates expression of sex-typical adult social behavior. As in SA1, we will induce expression of our representative sex-specific modules. We will then determine whether this is sufficient to increase expression of two sex-typical adult social behaviors, maternal behavior and territorial aggression as in SA2, in the absence of play. My sponsor is Dr. Margaret McCarthy, a leader in the field of brain sex differences, and my co-sponsor is Dr. Seth Ament, an expert in the functional genomics of social behavior. With their guidance, as well as my participation in targeted coursework and professional development activities, I will receive in-depth training in bioinformatics, functional genomics, and behavioral neuroscience that will enable my future success as an independent researcher.

项目概要社交游戏或打闹游戏是大多数哺乳动物所表现出的社会行为的特征模式尽管游戏的功能存在争议，但综合证据表明，游戏对于适当的社交至关重要。成年后的行为、认知和繁殖成功率重要的是，表达存在性别差异。男性比女性表现出更大的玩耍强度和频率，但存在个体差异；因为有些女性的游戏水平与男性的水平相当，而有些男性的水平则较低在最近的一项实验中，我们旨在利用这些个体差异的力量来获得新的见解。我们对与游戏相关的性别依赖和性别无关转录特征进行了一次评分。每天进行 4 天的实验，将每种性别中排名前三分之一的老鼠设计为“高玩”，将排名后三分之一的老鼠设计为“低玩”。玩耍”，从内侧杏仁核（MeA；玩耍男性化部位）收集组织进行 RNA 测序 (RNA-seq)，并使用加权基因共表达网络分析 (WGCNA) 来鉴定 22 个基因共表达表达模块，或协调调节基因的网络值得注意的是，除了 12 个模块之一之外的所有模块（对于 p<0.05）与游戏相关的表达具有性别特异性，表明转录组中存在性别差异与男性和女性的游戏相关的概况建立在之前的理论基础上，即游戏的功能是为了塑造能够表达成人行为的电路，我们的中心假设认为转录游戏表达的 MeA 网络具有性别特异性，因为幼年游戏会调节表达我们将使用两个具有代表性的特定性别、与游戏相关的模块来测试典型性别的成人社会行为。该假设跨越 3 个特定目标 (SA)，确定模块表达是否具有因果调节作用。为此，我们将测试过度表达模块调节器的效果。我们在 MeA 中具有代表性的性别特异性模块，并确定这是否会影响预测性别的游戏 SA2 仅将青少年游戏的表达与性别典型的成人社会行为的表达相关联，从而确定。如果嬉戏的个体差异与领地攻击性表达的差异（男性）有关最后，SA3 确定模块表达是否因果调节表达。与 SA1 一样，我们将诱导代表性性别特异性的表达。然后我们将确定这是否足以增加两种性别典型成人社交的表达。在没有玩耍的情况下，我的行为、母性行为和领土攻击行为。玛格丽特·麦卡锡 (Margaret McCarthy)，大脑性别差异领域的领导者，我的共同发起人是专家赛斯·阿门特 (Seth Ament) 博士在他们的指导下，以及我有针对性地参与社会行为的功能基因组学方面。课程作业和专业发展活动，我将接受生物信息学、功能学方面的深入培训基因组学和行为神经科学将使我未来作为一名独立研究员取得成功。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Maternal-fetal transmission of delta-9-tetrahydrocannabinol (THC) and its metabolites following inhalation and injection exposure during pregnancy in rats.

大鼠妊娠期间吸入和注射暴露后，δ9-四氢大麻酚（THC）及其代谢物的母胎传播。

DOI：
发表时间：
2022-03
期刊：
影响因子：
4.2
作者：
Baglot, Samantha L;VanRyzin, Jonathan W;Marquardt, Ashley E;Aukema, Robert J;Petrie, Gavin N;Hume, Catherine;Reinl, Erin L;Bieber, John B;McLaughlin, Ryan J;McCarthy, Margaret M;Hill, Matthew N
通讯作者：
Hill, Matthew N