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Functional ontogeny of pair bonding neural circuits

配对神经回路的功能个体发育

基本信息

批准号：
10704079
负责人：
Lisa Hiura
金额：
$ 37.15万
依托单位：
UNIVERSITY OF COLORADO
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：
2022-09-13 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10704079
关键词：
Adolescence Adolescent Adolescent Development Adult Age Agreement Animal Technicians Animals Appointment Attention deficit hyperactivity disorder Automobile Driving Award Basic Science Behavior Behavior Control Behavioral Paradigm Brain Cell physiology Cellular biology Color Colorado Core Facility Development Developmental Biology Disease Dopamine Dryness Embryonic Development Ensure Faculty Fellowship Female Fiber Foundations Functional disorder Funding Gene Expression Profile Gene Expression Regulation Genetic Genetic Transcription Goals Grant Growth HRK gene Health Health Benefit Home Imaging Techniques Impairment Individual Institution Knowledge Laboratories Laboratory Rat Laboratory mice Life Major Depressive Disorder Mediating Mentors Mentorship Microscopy Microtus Molecular Molecular Biology Motivation Neurodevelopmental Disorder Neurons Neurosciences Pair Bond Partner in relationship Pathogenesis Pathology Pharmacogenetics Phenotype Photometry Physiological Play Positioning Attribute Poverty Predisposition Principal Investigator Process Property Publications Rattus Recording of previous events Research Research Assistant Resources Rewards Risk Rodent Rodent Model Role Same-sex Schizophrenia Secure Shapes Signal Transduction Social Behavior Social Development Social Interaction Social Network Social isolation Stem Cell Research Support System System Technical Expertise Technology Therapeutic Time Translational Research Universities Viral Well in self Work autism spectrum disorder career data analysis pipeline design dopamine system experience forging functional outcomes genetic approach human model in vivo innovation insight instrumentation interest loved ones mature animal mesolimbic system neural neural circuit neuromechanism neuropsychiatric disorder neuropsychiatry neuroregulation novel optogenetics postnatal development prairie vole professor programs protective effect reward circuitry scaffold sex social social anxiety social attachment social deficits social engagement social neuroscience social skills therapeutic target

项目摘要

Project summary/Abstract The rewarding bonds we forge in adulthood, in particular our pair bonds with romantic partners, have innumerable protective effects on our brains and behaviors. Individuals with difficulties in social engagement and competence, such as those suffering from social anxiety, major depression, ADHD, or Autism Spectrum Disorder, are particularly susceptible to the health risks of social isolation and impoverished social networks. Aberrant activity of dopaminergic reward systems during adolescence coincides with the onset of many of these disorders, suggesting that developmental abnormalities in the neural substrates that promote social reward underlies disease pathology. Critically, most of what we know about the neural mechanisms that facilitate pair bonding come from the study of adult brains, highlighting a dire need to investigate the functional development of social bonding circuits to design better therapeutic treatments for social dysfunctions. The current proposal aims to leverage the socially monogamous prairie vole system to investigate the maturational changes in dopaminergic reward circuitry that initiate the capacity for pair bonding in adulthood. Prairie voles form strong pair bonds with their mates, which relies on the functional activity of dopamine systems. In Aim 1, I will use fiber photometry to ask how developmental age and sex mediates socially induced changes in in vivo dopaminergic neural activity. In Aim 2, I will use chemogenetic approaches to investigate how perturbing dopamine circuits during sensitive developmental periods impacts adult pair bonding phenotypes. Finally, in Aim 3 I will investigate the developmental changes in transcriptional signatures of same‐sex and opposite‐sex social interactions as prairie voles mature and become capable of dopamine‐dependent pair bonding. Altogether, these efforts will determine how social experiences across developmental time scaffold the maturation of pair bonding dopamine circuits. These findings will profer novel insights into the molecular and cellular processes that may be disrupted in neuropsychiatric illnesses involving impaired bonding behaviors, which cannot be investigated in traditional non‐bonding rodent models.

项目概要/摘要我们在成年后建立的有益纽带，特别是我们与浪漫伴侣的结对纽带，有无数的好处。对我们的大脑和行为的保护作用。在社会参与和能力方面有困难的个人，例如因为那些患有社交焦虑症、重度抑郁症、多动症或自闭症谱系障碍的人尤其容易容易受到社会孤立和贫困社交网络的健康风险的影响。多巴胺能异常活动青春期的奖励系统与许多此类疾病的发生同时发生，这表明发育促进社会奖赏的神经基质异常是疾病病理学的基础。关键的是，大部分我们通过对成人大脑的研究了解了促进配对联系的神经机制，强调了迫切需要研究社会联系回路的功能发展以设计更好的治疗方法对于社交功能障碍。目前的提案旨在利用社会一夫一妻制的草原田鼠系统研究多巴胺能奖励电路的成熟变化，这些变化启动了配对结合的能力成年期。草原田鼠与配偶形成牢固的配对关系，这依赖于多巴胺的功能活动系统。在目标 1 中，我将使用光纤光度测定来询问发育年龄和性别如何介导社会引起的变化体内多巴胺能神经活动。在目标 2 中，我将使用化学遗传学方法来研究扰动如何敏感发育时期的多巴胺回路会影响成年配对表型。最后，在目标 3 中我将研究同性和异性社交互动的转录特征的发展变化草原田鼠成熟并能够进行多巴胺依赖性配对。总而言之，这些努力将决定整个发育时期的社会经历如何促进配对多巴胺回路的成熟。这些研究结果将为神经精神病学中可能被破坏的分子和细胞过程提供新的见解涉及联结行为受损的疾病，这些疾病无法在传统的非联结啮齿动物模型中进行研究。