Sex-specific regulation of social play
社交游戏的性别特异性调节
基本信息
- 批准号:9120940
- 负责人:
- 金额:$ 25.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-09-23 至 2016-12-31
- 项目状态:已结题
- 来源:
- 关键词:AdolescenceAdolescentAmygdaloid structureAnimal ModelAreaAutistic DisorderBehaviorBrainCellsChildChildhoodDataDevelopmentDiseaseDopamineDrug TargetingElectrophysiology (science)FemaleFunctional disorderGlutamatesGoalsHealthImmunohistochemistryIncidenceKnowledgeLateralLifeMedialMediatingMental disordersMicrodialysisMicroinjectionsMissionModelingNational Institute of Mental HealthNeurodevelopmental DisorderNeuronsNeurotransmittersOutcomeOutputPathway interactionsPlayPublic HealthRattusRegulationResearchReverse Transcriptase Polymerase Chain ReactionRewardsRoleSeveritiesSex BiasSex CharacteristicsSiteSocial BehaviorSocial FunctioningSocial skills developmentStructure of terminal stria nuclei of preoptic regionSymptomsSystemTestingTherapeuticTherapeutic UsesV1a vasopressin receptorVasopressin ReceptorVasopressinsVentral Tegmental Areaautism spectrum disorderdopamine systemdopaminergic neurongamma-Aminobutyric Acidin vivoinnovationinterdisciplinary approachmaleneural circuitneuromechanismreceptorresponsereward circuitrysexsocialtreatment response
项目摘要
DESCRIPTION (provided by applicant): Social play activities during childhood and adolescence are important for the development of social skills needed throughout life. Social play is a highly rewarding activity and is modulated by the mesocorticolimbic dopamine system. Social play deficits are a core symptom of neurodevelopmental disorders such as autism spectrum disorders (ASD). ASD and other neurodevelopmental disorders further show robust sex differences in incidence, symptom severity, and treatment responses. The vasopressin (VP) system is important for the regulation of social behaviors, is sexually dimorphic (males have more VP than females), shows abnormalities in ASD, and emerges as potential drug target in the treatment of social dysfunction. Understanding how VP regulates social behaviors during development and in both sexes is therefore essential. The long-term goal of this research is to reveal the neural circuitry by which VP regulates social play in both sexes. We use rats as model organism because social play is well defined in rats and the sexually dimorphic VP system is highly conserved across mammalian species. The overall hypothesis is that the LS-VP system is involved in sex- specific regulation of social play via its interactions with the brai reward system. In support, we showed that blockade of the VP V1a receptor (V1aR; main VP receptor in the brain) in the lateral septum (LS) enhances social play in males, but decreases it in females. This suggests that VP released in the LS inhibits social play in males, but stimulates social play in females. The objective is to identify the sex-specific neuronal mechanisms and the interaction of VP with the brain reward circuitry in the regulation of social play in juvenile rats We will build on these findings and aim to identify the mechanisms in the LS by which VP modulates social play in sex-specific ways (Aim 1) and determine whether VP acts through the LS-VTA pathway to modulate social play in sex-specific ways (Aim 2). The two independent specific aims will collectively reveal how the LS- VP system modulates major neurotransmitter systems in the LS and in the ventral tegmental area (VTA, site of origin of the mesocorticolimbic dopamine system) to regulate social play in sex-specific ways. Aim 1 will test the hypothesis that VP mediates sex differences in LS neuronal activity during social play. Aim 2 will test the hypothesis that VP mediates sex differences in the LS-VTA pathway during social play. This proposal is innovative because it will identify sex-specific neural mechanisms underlying the regulation of behavior, and it will reveal the involvement of the LS-VTA pathway in social reward behavior, and it will use a comprehensive multidisciplinary approach to examine the LS-VP system and its interactions with the VTA system in a unique and integrated way. The proposed research is significant because outcomes will be informative for understanding the potential role of VP in sex-specific regulation of typical and atypical social play in children.
描述(由申请人提供):儿童和青少年时期的社交游戏活动对发展一生所需的社交技能非常重要。社交游戏是一种高回报的活动,并受到中皮质边缘多巴胺系统的调节。社交游戏缺陷是自闭症谱系障碍(ASD)等神经发育障碍的核心症状。ASD和其他神经发育障碍在发病率、症状严重程度和治疗反应方面进一步显示出强大的性别差异。血管加压素(VP)系统对于社会行为的调节是重要的,是性二态的(男性比女性具有更多VP),在ASD中显示异常,并且在治疗社会功能障碍中成为潜在的药物靶点。因此,了解VP如何在发育过程中调节两性的社会行为至关重要。这项研究的长期目标是揭示VP调节两性社交游戏的神经回路。我们使用大鼠作为模式生物,因为社会发挥是很好地定义在大鼠和性二态VP系统是高度保守的哺乳动物物种。总体假设是,LS-VP系统通过与大脑奖励系统的相互作用参与社会游戏的性别特异性调节。作为支持,我们发现,阻断外侧隔(LS)中的VP V1 a受体(V1 aR;大脑中的主要VP受体)增强了男性的社交游戏,但降低了女性的社交游戏。这表明,VP释放在LS抑制社会发挥男性,但刺激社会发挥女性。目的是确定性特异性的神经元机制和VP的相互作用与大脑奖赏回路在调节社会游戏在幼年大鼠我们将建立在这些发现,并旨在确定的机制,在LS VP调制社会游戏的性别特异性的方式(目的1),并确定VP是否通过LS-VTA通路的行为,以调节社会游戏的性别特异性的方式(目的2)。这两个独立的具体目标将共同揭示LS-VP系统如何调节LS和腹侧被盖区(VTA,中皮质边缘多巴胺系统的起源部位)中的主要神经递质系统,以调节性别特异性方式的社会游戏。目的1将测试的假设,VP介导的性别差异LS神经元活动在社会发挥。目的2将测试的假设,VP介导的LS-VTA通路的性别差异,在社会发挥。这项建议是创新的,因为它将确定行为调节的性别特异性神经机制,它将揭示LS-VTA通路在社会奖励行为中的参与,它将使用一种全面的多学科方法来研究LS-VP系统及其与VTA系统的相互作用。拟议的研究是显着的,因为结果将是翔实的了解VP的性别特异性调节的典型和非典型的社会发挥儿童的潜在作用。
项目成果
期刊论文数量(0)
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Alexandra H. Veenema其他文献
Alexandra H. Veenema的其他文献
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{{ truncateString('Alexandra H. Veenema', 18)}}的其他基金
Oxytocin neural circuitry involvement in juvenile social play
催产素神经回路参与青少年社交游戏
- 批准号:
10590706 - 财政年份:2022
- 资助金额:
$ 25.04万 - 项目类别:
Oxytocin neural circuitry involvement in juvenile social play
催产素神经回路参与青少年社交游戏
- 批准号:
10363314 - 财政年份:2022
- 资助金额:
$ 25.04万 - 项目类别:
Sex and age differences in the regulation of social recognition
社会认可调节中的性别和年龄差异
- 批准号:
8626679 - 财政年份:2014
- 资助金额:
$ 25.04万 - 项目类别:
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