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:
- 金额:$ 37.15万
- 依托单位:
- 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:
- 关键词:AdolescenceAdolescentAdolescent DevelopmentAdultAgeAgreementAnimal TechniciansAnimalsAppointmentAttention deficit hyperactivity disorderAutomobile DrivingAwardBasic ScienceBehaviorBehavior ControlBehavioral ParadigmBrainCell physiologyCellular biologyColorColoradoCore FacilityDevelopmentDevelopmental BiologyDiseaseDopamineDrynessEmbryonic DevelopmentEnsureFacultyFellowshipFemaleFiberFoundationsFunctional disorderFundingGene Expression ProfileGene Expression RegulationGeneticGenetic TranscriptionGoalsGrantGrowthHRK geneHealthHealth BenefitHomeImaging TechniquesImpairmentIndividualInstitutionKnowledgeLaboratoriesLaboratory RatLaboratory miceLifeMajor Depressive DisorderMediatingMentorsMentorshipMicroscopyMicrotusMolecularMolecular BiologyMotivationNeurodevelopmental DisorderNeuronsNeurosciencesPair BondPartner in relationshipPathogenesisPathologyPharmacogeneticsPhenotypePhotometryPhysiologicalPlayPositioning AttributePovertyPredispositionPrincipal InvestigatorProcessPropertyPublicationsRattusRecording of previous eventsResearchResearch AssistantResourcesRewardsRiskRodentRodent ModelRoleSame-sexSchizophreniaSecureShapesSignal TransductionSocial BehaviorSocial DevelopmentSocial InteractionSocial NetworkSocial isolationStem Cell ResearchSupport SystemSystemTechnical ExpertiseTechnologyTherapeuticTimeTranslational ResearchUniversitiesViralWell in selfWorkautism spectrum disordercareerdata analysis pipelinedesigndopamine systemexperienceforgingfunctional outcomesgenetic approachhuman modelin vivoinnovationinsightinstrumentationinterestloved onesmature animalmesolimbic systemneuralneural circuitneuromechanismneuropsychiatric disorderneuropsychiatryneuroregulationnoveloptogeneticspostnatal developmentprairie voleprofessorprogramsprotective effectreward circuitryscaffoldsexsocialsocial anxietysocial attachmentsocial deficitssocial engagementsocial neurosciencesocial skillstherapeutic 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。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Lisa Hiura其他文献
Lisa Hiura的其他文献
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{{ truncateString('Lisa Hiura', 18)}}的其他基金
Functional ontogeny of pair bonding neural circuits
配对神经回路的功能个体发育
- 批准号:
10481368 - 财政年份:2022
- 资助金额:
$ 37.15万 - 项目类别:
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