Maturation of somatosensory circuits for social behaviors

项目摘要/摘要 触摸对亲子互动有很大贡献，而这种互动是早期社会发展的基础。 在婴儿出生时最发达的感觉方式中，触摸继续在 在整个发育和成年生活中的沟通和社会互动。触觉知觉异常 是自闭症谱系障碍(ASD)患者的普遍特征，加剧了核心社会缺陷。 而触觉感觉加工与社会行为之间的关系已被广泛研究 从临床角度使用心理物理范式，对神经生物学机制知之甚少。 它们之间的联系，以及它们如何促进彼此的发展。了解社交功能如何 与早期的触觉感觉输入一起编码将为电路的出现提供有价值的见解 整合初级感觉加工和高级认知功能。 通过三个不同的目标，我们建议利用纵向双光子成像、遗传工具和行为 催产素是一种在广泛的社会行为中至关重要的神经肽，它是如何调节表面的 神经元间回路促进社交触觉的发展。我们选择关注涉及L1的电路 Reelin表达(L1Re)中间神经元在限制锥体神经元中的独特连接和功能 在出生后早期感觉输入时的激活。在目标1中，我们将调查表达 桶状皮质浅层的催产素受体(OXTRs)，并确定催产素的功能。 涉及L1Re中间神经元的调制电路。在目标2中，我们将检测新生儿体内神经元的活动。 在DAM期间，小鼠幼鼠诱导社交接触，并确定L1中催产素信号的中断是如何 中间神经元影响这种活动。在目标3中，我们将扩展我们对催产素在高血压发生中的作用的研究。 社会接触，涵盖从新生儿阶段到成年的整个发育时期，通过执行纵向 双光子成像，完成了对这段时间内社会互动的长期行为评估。 综合起来，这些目标将揭示中间神经元如何塑造社会互动，提供一个有助于 完善治疗ASD症状和其他神经发育障碍的治疗方向。 通过解决这些问题并执行拟议的工作，候选人将构建技术和 专业技能将为未来的独立研究人员职业生涯奠定坚实的基础。共同导师， De Marco García博士和Froemke博士将在概念设计和设计的正式方面监督候选人 通过定期会议进行实验方法(见培训计划)，并建议和支持候选人在 获得教员职位、建立独立实验室和获得初始资金的过程。忠告 委员会，由利斯顿、李和拉贾迪亚克沙博士组成，他们对这种方法有丰富的经验 研究战略纲要，将就研究的进行和解释提供咨询，并 在学术环境中驾驭早期研究的专业图景。

PROJECT SUMMARY/ABSTRACT Touch contributes powerfully to parent-infant interactions that are fundamental for early social development. Among the most developed sensory modalities when infants are born, touch continues to play a critical role in communication and social interaction throughout development and adult life. Abnormalities in tactile perception are prevalent features in individuals with autism spectrum disorders (ASD), exacerbating the core social deficits. While the relationship between tactile sensory processing and social behaviors have been studied extensively using psychophysical paradigms from clinical perspectives, little is known about the neurobiological mechanisms underlying their link, and how they facilitate the development of one another. Understanding how social features are encoded alongside early tactile sensory inputs will provide valuable insights into the emergence of circuits integrating primary sensory processing and higher-order cognitive features. Through three distinct aims, we propose to leverage longitudinal two-photon imaging, genetic tools and behavioral assays to determine how oxytocin, a neuropeptide critical in a wide range of social behaviors, modulates superficial interneuronal circuits to facilitate the development of social touch. We choose to focus on the circuits involving L1 reelin-expressing (L1 Re) interneurons due to their unique connectivity and function in restricting pyramidal neuron activation during sensory input in early postnatal days. In Aim 1, we will survey the neuronal types that express oxytocin receptors (OXTRs) in the superficial layers of the barrel cortex, and determine the function of oxytocin in modulating circuits involving L1 Re interneurons. In Aim 2, we will examine the in vivo neuronal activity in neonatal mouse pups during dam induced social touch, and determine how disruption in oxytocin signaling in L1 Re interneurons affects this activity. In Aim 3, we will extend our investigation on the role of oxytocin in the emergence of social touch to cover the entire developmental time period from neonatal stage to adulthood by performing longitudinal two-photon imaging, completed with long-term behavioral assessment of social interaction over this time span. Together, these aims will reveal how interneurons shape social interaction, providing a framework that can help refine therapeutic directions for treating symptoms of ASD as well as other neurodevelopmental disorders. By addressing these questions and carrying out the proposed work, the candidate will build both technical and professional skills that will provide a solid foundation for a future career as an independent researcher. The co-mentors, Drs. De Marco García and Froemke, will supervise the candidate in formal aspects of conceptual design and experimental methods through regular meetings (see Training Plan) and also advise and support the candidate in the process of securing a faculty position, setting up an independent lab, and securing initial funding. The Advisory Committee, which consists of Drs. Liston, Lee and Rajadhyaksha, who have extensive experience with the methods outlines in the Research Strategy, will provide consultation on both the conduct and interpretation of the research and in navigating the professional landscape of early-stage research in an academic setting.