Cell-type and projection-specific dissection of the bed nucleus of the stria terminalis in the mediation of social behavioral deficits induced by early life adversity

终纹床核的细胞类型和投射特异性解剖在调节早期生活逆境引起的社会行为缺陷中的作用

基本信息

批准号：
10816152
负责人：
Lindsay Renee Halladay
金额：
$ 8.14万
依托单位：
SANTA CLARA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2023-11-30
项目状态：
已结题

项目摘要

PROJECT SUMMARY Nearly one percent of children in the US experience childhood abuse or neglect, which can induce life-long behavioral deficits including social behavior disorders like social anxiety, attachment disorders, difficult peer relations, and externalizing behaviors. Investigations into the neural mechanisms mediating early life adversity induced behavioral impairments have largely focused on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and its release of the stress hormone corticotropin-releasing factor (CRF), which accounts for aspects of altered anxiety and responsiveness to stress induced by early life adversity. However, social interaction involves coordination between neural circuits promoting reward and circuits inhibiting anxiety, and thus neural substrates mediating early life adversity-induced social deficits likely extend beyond HPA axis dysfunction, but this has not been systematically investigated. Our parent grant is designed to address the extent to which early adversity-induced social deficits are driven by dysfunction in anxiety versus reward circuits, critical for effectively treating disorders spurred by childhood abuse and neglect. Our lab uses mouse maternal separation with early weaning (MSEW) to model early life adversity, which robustly reduces social interaction and increases anxiety-like behavior, recapitulating effects of childhood abuse and neglect. Prior findings in my and others’ labs have consistently shown that rodent maternal separation procedures adversely affect females to a greater extent than males. This mirrors the human clinical population, as females exhibit greater rates of anxiety-related disorders and depression than males. While research for the parent grant considers sex as an experimental factor, we have devised a study to further examine how exposure to early life adversity interferes with the development of sexually dimorphic neuronal systems to permanently alter behavior. Ms. Janet Ronquillo will carry out this experimentation during a post-baccalaureate gap year, during which she will also follow a rigorous plan to set her up for success in her future career path.

项目概要美国近百分之一的儿童在童年时期经历过虐待或忽视，这可能导致终身行为缺陷，包括社交行为障碍，如社交焦虑、依恋障碍、难以相处的同伴关系和外化行为的研究介导早期生活逆境的神经机制。诱发的行为障碍主要集中在下丘脑-垂体-肾上腺的失调（HPA）轴及其释放的应激激素促肾上腺皮质激素释放因子（CRF），它解释了然而，早期生活逆境引起的焦虑和对压力的反应发生了变化。相互作用涉及促进奖励的神经回路和抑制焦虑的神经回路之间的协调，以及因此，调节早年逆境引起的社交缺陷的神经基质可能会超出 HPA 轴功能障碍，但这尚未得到系统的调查，我们的家长拨款旨在解决这个问题。早期逆境引起的社会缺陷在多大程度上是由焦虑与奖励功能障碍引起的电路，对于有效治疗儿童虐待和忽视引起的疾病至关重要我们的实验室使用鼠标。母亲早期断奶分离（MSEW）来模拟早期生活的逆境，这大大减少了社会互动并增加类似焦虑的行为，重现童年虐待和忽视的影响。我和其他人实验室的研究结果一致表明，啮齿动物母体分离程序对正如女性所表现的那样，这反映了人类临床人群。与男性相比，焦虑相关疾病和抑郁症的发病率更高。将性视为一个实验因素，我们设计了一项研究来进一步检验早期生活中的暴露程度逆境会干扰性二态性神经系统的发育，从而永久改变 Janet Ronquillo 女士将在学士学位后的间隔年期间进行这项实验。她还将遵循严格的计划，为她未来的职业道路取得成功做好准备。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nature and nurture: comparing mouse behavior in classic versus revised anxiety-like and social behavioral assays in genetically or environmentally defined groups.

先天与后天：在遗传或环境定义的群体中，比较经典与修订的焦虑样和社会行为测定中的小鼠行为。

DOI：
10.1101/2023.06.16.545212
发表时间：
2023
期刊：
bioRxiv : the preprint server for biology
影响因子：
0
作者：
Ronquillo,Janet;Nguyen,MichaelT;Rothi,Linnea;Bui-Tu,Trung-Dan;Yang,Jocelyn;Halladay,LindsayR
通讯作者：
Halladay,LindsayR