Breaking bonds in prairie voles

打破草原田鼠的束缚

基本信息

批准号：
10581709
负责人：
MOHAMED KABBAJ
金额：
$ 60.07万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-01 至 2026-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10581709
关键词：
Acute Aggressive behavior Animal Model Anxiety Area Behavior Brain Buffers CRISPR/Cas technology Cardiovascular system Cells Chronic Data Dopamine Dopamine D1 Receptor Dopamine D2 Receptor Enterobacteria phage P1 Cre recombinase Female Foundations Friends Gene Expression Genes Globus Pallidus Human Immune system Knock-in Life Stress Maintenance Mediating Mental Depression Microtus Moods Neurons Nucleus Accumbens Oxytocin Oxytocin Receptor Pair Bond Pathology Pathway interactions Pharmaceutical Preparations Play Receptor Gene Role Side Sleep disturbances Social Behavior Social isolation Stress Structure System Ventral Tegmental Area Work biological adaptation to stress dysphoria follow-up genetic approach genome editing hypothalamic-pituitary-adrenal axis male neurochemistry paraventricular nucleus postsynaptic prairie vole preference presynaptic psychostimulant response sex single cell sequencing social social attachment stress management transcriptomics

项目摘要

In humans, social attachment with partners, relatives, or friends act as a protective buffer against many negative consequences of life stress, whereas lack of social attachments can lead to serious pathologies including dysphoria, anxiety, depression, sleep disturbance, cardiovascular problems, and immune system deficits. In the social prairie voles, acute and chronic social isolation as well as partner separation induce anxiety and depression-like behaviors, enhance stress response, and alter activities of several neurochemical systems, including the oxytocinergic system. Data from our group and others have shown that oxytocin (OT) is involved not only in the formation of pair bonds in this specie, but also in the response to social isolation/ partner separation as well as social buffering of stress responses. In this proposal, we will verify the overall hypothesis that breaking bonds in voles alter the OT circuitry projecting from the hypothalamic PVN to the nucleus accumbens (which represents 90% of OT projections to nucleus accumbens) and leads to negative consequences on social behaviors in male and female prairie voles.

对于人类来说，与伴侣、亲戚或朋友的社会依恋可以起到保护缓冲作用生活压力会带来许多负面后果，而缺乏社交依恋可能会导致严重的病症，包括烦躁、焦虑、抑郁、睡眠障碍、心血管疾病问题和免疫系统缺陷。在社会性草原田鼠中，急性和慢性社会性孤立以及伴侣分离会诱发焦虑和抑郁样行为，增强应激反应，并改变几个神经化学系统的活动，包括催产素系统。我们小组和其他人的数据表明，催产素 (OT) 不仅参与在这个物种中形成配对纽带，而且也体现在对社会孤立/伴侣的反应中分离以及压力反应的社会缓冲。在本提案中，我们将验证总体假设是，破坏田鼠体内的化学键会改变从下丘脑 PVN 到伏隔核（代表 90% 的 OT 投射到伏隔核）伏隔核）并对雄性和雌性草原的社会行为产生负面影响田鼠。