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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

基本信息

批准号：
8626679
负责人：
Alexandra H. Veenema
金额：
$ 46.95万
依托单位：
BOSTON COLLEGE
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：
2014-01-15 至 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8626679
关键词：
Adolescent Adult Age Animal Model Animals Area Autistic Disorder Behavior Behavioral Brain Detection Disease Drug Targeting Early Diagnosis Female Fiber Functional disorder Goals Human Immunohistochemistry Incidence Individual Injection of therapeutic agent Knowledge Lateral Life Light Link Maps Measures Mental disorders Microdialysis Microinjections Mission National Institute of Mental Health Neurodevelopmental Disorder Neurons Neurosciences Outcome Output Oxytocin Oxytocin Receptor Pathway interactions Procedures Public Health Rattus Regulation Research Role Severities Sex Bias Sex Characteristics Social Behavior Social Controls Social Interaction Staging Students Symptoms System Techniques Testing Therapeutic Uses Time Training Translating V1a vasopressin receptor Vasopressin Receptor Vasopressins Vertebrates age difference autism spectrum disorder base density improved in vivo innovation insight male nerve supply neural circuit novel preference public health relevance receptor binding relating to nervous system response sex social treatment response

项目摘要

7. PROJECT SUMMARY Social recognition (the ability to discriminate between familiar and unfamiliar individuals) is essential for appro- priate and beneficial social interactions. Conversely, social recognition deficits are observed in autism spec- trum disorders (ASD). ASD is diagnosed early in life and shows a strong male-bias in incidence and symptom severity. This drives the need to understand the neural basis of social recognition and to study this in both sex- es and at an early age. The vasopressin (VP) and oxytocin (OT) systems are ideal candidates to study the neural basis of social recognition because they modulate social recognition in humans and animals, show sex and age differences in the brain, have been implicated in ASD, and emerge as potential drug targets in the treatment of social dysfunction. The long-term goal of this research is to reveal the neuronal mechanisms and pathways by which VP and OT regulate social recognition in both sexes and at both juvenile and adult ages. We will use rats as model organism because social recognition is well defined in rats and the VP and OT sys- tems are highly conserved across mammalian species. The overall hypothesis is that VP and OT systems function differently in both sexes and at both ages to regulate social recognition. In support, we showed that administration of VP into the lateral septum (LS) improves social recognition in juvenile females, but not in ju- venile males. Moreover, blockade of the VP V1a receptor (V1aR; main VP receptor in the brain) impaired so- cial recognition in adult males and females while it induced a preference to investigate a familiar rat over a novel rat in juvenile males and females. The objective is to determine how VP and OT in the LS regulate social recognition in sex- and age-specific ways. There are three independent specific aims that collectively will pro- vide insights into the mechanisms and pathways by which VP and OT regulate social recognition. Aim 1 will test the hypothesis that differential LS-VP release underlies sex and age differences in the regulation of social recognition. Aim 2 will test the hypothesis that OT regulates social recognition in sex- and age-specific ways. Aim 3 will test the hypothesis that VP and OT in the LS regulate social recognition via sex- and age-specific modulation of LS projection areas. We will use a comprehensive approach that includes in vivo microdialysis, microinjections, anatomical pathway tracing, mapping of neuronal responses, and behavioral analysis. This approach is innovative because this will be the first comprehensive study comparing neuropeptidergic control of social recognition between the sexes and at two life stages. The proposed research is significant because VP and OT regulate social recognition in humans and outcomes may therefore have translational potential for understanding sex and age differences in the roles of VP and OT in normal and abnormal social recognition in humans.

7.项目摘要社会识别（区分熟悉和不熟悉的人的能力）对于正确的人来说是必不可少的。私人的和有益的社会交往。相反，在自闭症患者中观察到社会认知缺陷，心房紊乱（ASD）。ASD在生命早期被诊断出来，并且在发病率和症状方面表现出强烈的男性偏见严重性。这就需要了解社会识别的神经基础，并在两性中研究这一点- 和在早期的年龄。后叶加压素（VP）和催产素（OT）系统是研究垂体后叶激素分泌的理想候选系统。社会认知的神经基础，因为它们调节人类和动物的社会认知，和大脑中的年龄差异，与ASD有关，并成为治疗ASD的潜在药物靶点。治疗社会功能障碍。这项研究的长期目标是揭示神经机制， VP和OT调节两性以及青少年和成年人社会认知的途径。我们将使用大鼠作为模型生物体，因为大鼠的社会识别是明确的，VP和OT系统- TEM在哺乳动物物种中高度保守。总的假设是VP和OT系统在两性和两个年龄段调节社会认可的功能不同。作为支持，我们表明，将VP注入外侧隔（LS）可改善青少年女性的社会认知，但对青少年女性没有影响。卑鄙的男性此外，阻断VP V1 a受体（V1 aR;大脑中的主要VP受体）会损害成年雄性和雌性的社会识别，而它诱导偏好调查熟悉的老鼠，而不是一个幼龄雄性和雌性中的新型大鼠。目的是确定VP和OT在LS中如何调节社会以性别和年龄为特征的方式获得认可。有三个独立的具体目标，共同将有利于- 通过VP和OT调节社会认知的机制和途径，提供了深入的见解。目标1将检验LS-VP释放差异是社会调节中性别和年龄差异的基础这一假设识别.目标2将测试的假设，OT调节社会认可的性别和年龄的具体方式。目的3将检验假设，即VP和OT在LS调节社会承认通过性别和年龄特异性 LS投影区域的调制。我们将使用一种综合的方法，包括体内微透析，显微注射、解剖路径追踪、神经元反应的映射和行为分析。这方法是创新的，因为这将是第一个全面的研究比较神经肽能控制在两个生命阶段中两性之间的社会认同。这项研究意义重大，因为 VP和OT调节人类的社会认知，因此结果可能具有转化潜力，了解VP和OT在正常和异常社会认知中作用的性别和年龄差异，人类