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.

项目摘要在美国，近1％的儿童经历了童年时期的虐待或忽视，这可能会诱发终身行为定义包括社交行为障碍，例如社交动画，依恋障碍，困难的同伴关系和外在行为。调查介导早期生活广告的神经机制诱导的行为障碍主要集中于下丘脑 - 垂体 - 肾上腺的失调（HPA）轴及其释放应力同性皮质激素释放因子（CRF），该系数解释了早期广告引起的焦虑和对压力的反应改变的方面。但是，社交互动涉及促进奖励和抑制动画电路的神经回路之间的协调，以及因此，介导早期生活广告引起的社会缺陷的神经底物可能超出HPA轴功能障碍，但这尚未系统地研究。我们的父母赠款旨在解决早期广告引起的社会缺陷是由动画与奖励的功能障碍所驱动的电路，对于有效治疗儿童虐待和忽视所激发的疾病至关重要。我们的实验室使用鼠标与早期断奶（MSEW）的孕产妇分离，以建模早期生活逆境，从而稳固地减少社会互动并增加类似焦虑的行为，概括儿童虐待和忽视的影响。事先的我和其他人的实验室中的发现始终表明啮齿动物的材料分离程序是不利的比男性更大程度地影响女性。这反映了人类临床人群，因为女性表现出与男性相比，与焦虑有关的疾病和抑郁症的比率更高。同时为父母赠款进行研究将性视为实验因素，我们设计了一项研究，以进一步研究如何暴露于早期生活逆境干扰性二态神经元系统的发展以永久改变行为。珍妮特·隆基洛（Janet Ronquillo）女士将在后期的差距年度进行此实验她还将遵循一项严格的计划，以在未来的职业道路上为她取得成功。

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