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.

项目摘要/摘要我们在成年期建立的有益的纽带，尤其是我们的夫妻与浪漫伴侣的纽带，有无数对我们的大脑和行为的保护作用。社会参与和能力困难的人，由于患有社交焦虑，严重抑郁症，多动症或自闭症谱系障碍的人尤其是容易受到社会隔离和社交网络贫困的健康风险。多巴胺能的异常活性青少年期间的奖励系统与许多此类疾病的发作相吻合，这表明发展促进社会奖励的神经底物的异常是疾病病理学的基础。至关重要的是，大多数我们知道神经机制快乐成对的结合来自对成年大脑的研究，强调了 DERE需要调查社会纽带电路的功能发展，以设计更好的治疗治疗用于社会功能障碍。当前的建议旨在利用社会一夫一妻制的草原vole系统研究启动配对键的能力的多巴胺能奖励电路的成熟变化成年。大草原田鼠与伴侣形成强大的配对键，这取决于多巴胺的功能活性系统。在AIM 1中，我将使用纤维光度法来询问发展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性。在AIM 2中，我将使用化学发生方法研究如何扰动敏感发育期间的多巴胺回路会影响成年对键合表型。最后，在目标3中，我会研究同性和相反社会互动的转录特征的发展变化草原田鼠成熟，并能够依赖多巴胺依赖性键合。这些努力总共确定在发育时期的社会经历如何脚手架成对的多巴胺电路的成熟。这些发现将使可能在神经精神病学中破坏的分子和细胞过程中提供新的见解疾病涉及粘结行为受损，这在传统的非束缚啮齿动物模型中无法研究。