Neural mechanisms of social status during adolescence

青春期社会地位的神经机制

• 批准号: 1937335
• 负责人: Brian Trainor
• 金额: $ 65万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1937335&HistoricalAwards=false
• 关键词: Neural; mechanisms; social; status; during

In animals including humans, winning a competitive encounter increases the chances of winning in future contests while losing increases the chance losing again in the future. These effects occur because the experience of winning and losing have different effects on the brain. What these discoveries do not explain, is how individuals can transition from losing to winning. This is especially true during adolescence, when individuals have less competitive experience and are more likely to lose. A specific type of behavioral strategy, social vigilance, may be a key mechanism for facilitating this transition. Social vigilance involves a combination of avoidance and observation of potentially threatening individuals. In this project, the research team will test whether increased testosterone secretion during adolescence facilitates a transition from social vigilance to more assertive aggressive behaviors in males. In adults, short term increases in testosterone after winning play a key role in facilitating winner effects. The researchers predict that the testosterone secretion during adolescence desensitizes neural circuits that promote social vigilance. To address this question this project will determine whether testosterone acts during puberty to alter the activity of neurons within neural circuits that control social vigilance as well as defensive and offensive vocalizations used in aggressive encounters. The University of California at Davis is a Hispanic Serving Institution with a strong track record of supporting an inclusive STEM culture to broaden impact and increase discovery. Support of this research will provide training opportunities for historically disadvantaged groups in STEM and increase community engagement via open house events.This project integrates behavioral, neuroendocrine, and physiological levels of analysis of social behavior. Previous work shows that oxytocin acting in the bed nucleus of the stria terminalis (BNST) increases social vigilance behavior, and that social stress increases the activity of oxytocin neurons. A key hypothesis is that the pubertal surge of testosterone reprograms oxytocin neurons in the BNST to be less sensitive to social stress. Social vigilance is oxytocin dependent, and more prevalent in juvenile males than adults. This research will first test whether increased testosterone during puberty reduces stress-induced vigilance in males and females. The effects of stress on long term potentiation (LTP) of oxytocin neurons will be examined and whether the effects of stress on LTP are modulated by pubertal testosterone exposure. In the rat hippocampus and the zebra finch song control system testosterone acts during puberty to reduce LTP. Finally, the effects of pubertal testosterone on territory formation will be studied by observing aggressive behaviors and the use of well characterized assertive and passive vocalizations during territory formation. Results from these studies will provide important insights into the neural circuits that facilitate social transitions that occurs across vertebrate species. This project will also generate new tools, including a brain atlas of the adolescent California mouse brain which will be hosted on brainmaps.org.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.

在包括人类在内的动物中，赢得一场竞争性比赛会增加在未来比赛中获胜的机会，而输掉比赛则会增加未来再次失败的机会。这些效应的产生是因为输赢的经历对大脑有不同的影响。这些发现没有解释的是，个人如何从失败过渡到成功。这一点在青春期尤其如此，此时个人竞争经验较少，更有可能失败。一种特定类型的行为策略，即社会警惕，可能是促进这一转变的关键机制。社会警惕包括对潜在威胁个人的回避和观察相结合。在这个项目中，研究小组将测试青春期睾酮分泌增加是否有助于男性从社会警惕向更自信的攻击性行为转变。对于成年人来说，获奖后睾丸激素的短期增加在促进获胜者效应方面发挥了关键作用。研究人员预测，青春期的睾丸素分泌会使促进社会警惕的神经回路变得不敏感。为了解决这个问题，这个项目将确定睾丸激素在青春期是否会改变神经回路中神经元的活动，这些神经回路控制着社会警惕以及在攻击性接触中使用的防御性和攻击性发声。加州大学戴维斯分校是一所拉美裔服务机构，在支持包容性STEM文化以扩大影响和增加发现方面有着良好的记录。这项研究的支持将为STEM中的历史弱势群体提供培训机会，并通过开放活动增加社区参与。该项目整合了对社会行为的行为、神经内分泌和生理层面的分析。以往的工作表明，作用于终纹床核(BNST)的催产素增加了社会警惕行为，而社会应激增加了催产素神经元的活动。一个关键的假设是，青春期睾丸激素的激增重新编程了BNST中的催产素神经元，使其对社会压力不那么敏感。社会警戒依赖于催产素，在青少年男性中比成年人更普遍。这项研究将首先测试青春期增加的睾丸素是否会降低男性和女性因压力而产生的警觉性。我们将研究应激对催产素神经元长时程增强(LTP)的影响，以及应激对LTP的影响是否受青春期睾酮的调节。在大鼠的海马体和斑马雀的鸣叫控制系统中，睾丸素在青春期起作用，以减少LTP。最后，将通过观察攻击性行为和在领土形成过程中使用典型的肯定和被动发声来研究青春期睾丸素对领土形成的影响。这些研究的结果将为促进脊椎动物物种间的社会转变的神经回路提供重要的见解。该项目还将产生新的工具，包括将在Brainmaps.org上托管的加州青少年老鼠大脑的脑图集。该奖项反映了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。

项目成果

Sexual differentiation of neural mechanisms of stress sensitivity during puberty.

• DOI: 10.1073/pnas.2306475120
• 发表时间: 2023-10-24
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Wright, Emily C.;Luo, Pei X.;Zakharenkov, Hannah C.;Godoy, Alexandra Serna;Lake, Alyssa A.;Prince, Zhana D.;Sekar, Shwetha;Culkin, Hannah I.;Ramirez, Alison, V;Dwyer, Tjien;Kapoor, Amita;Corbett, Cody;Tian, Lin;Fox, Andrew S.;Trainor, Brian C.
• 通讯作者: Trainor, Brian C.

Impacts of sex differences on optogenetic, chemogenetic, and calcium-imaging tools

• DOI: 10.1016/j.conb.2023.102817
• 发表时间: 2023-12-01
• 期刊: CURRENT OPINION IN NEUROBIOLOGY
• 影响因子: 5.7
• 作者: Salazar，Valentina I. Cea;Perez，Melvin D.;Trainor，Brian C.
• 通讯作者: Trainor，Brian C.