Maturation of somatosensory circuits for social behaviors

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形式中，触摸在整个发育和成年生活的交流和社会互动中继续发挥关键作用。触觉异常是自闭症谱系障碍(ASD)患者的普遍特征，加剧了核心的社会缺陷。虽然从临床角度利用心理物理范式对触觉感觉加工和社会行为之间的关系进行了广泛的研究，但对它们之间联系的神经生物学机制以及它们如何促进彼此发展的了解很少。了解社交功能是如何与早期触觉感觉输入一起编码的，将为整合初级感觉处理和更高阶认知功能的电路的出现提供有价值的见解。通过三个不同的目标，我们建议利用纵向双光子成像、遗传工具和行为分析来确定催产素是如何调节表层神经元内回路以促进社交触摸的发展的。催产素是一种在广泛的社会行为中至关重要的神经肽。我们选择关注涉及L1reelin表达(L1re)中间神经元的回路，因为它们在出生后早期的感觉输入中具有独特的连通性和限制锥体神经元激活的功能。在目标1中，我们将调查桶状皮质浅层表达催产素受体(OXTRs)的神经元类型，并确定催产素在涉及L1Re中间神经元的调制回路中的作用。在目标2中，我们将检测在DAM诱导的社会接触中新生小鼠体内神经元的活动，并确定L1Re中间神经元中催产素信号的中断如何影响这种活动。在目标3中，我们将通过进行纵向双光子成像，将我们对催产素在社交触摸出现中的作用的研究扩展到从新生儿阶段到成年的整个发育时期，并在这一时间跨度内完成对社交互动的长期行为评估。总之，这些目标将揭示中间神经元如何塑造社会互动，提供一个框架，有助于完善治疗ASD症状以及其他神经发育障碍的治疗方向。通过解决这些问题和执行拟议的工作，候选人将建立技术和专业技能，为未来的独立研究人员职业生涯奠定坚实的基础。联合导师De Marco García博士和Froemke博士将通过定期会议(参见培训计划)在概念设计和实验方法的正式方面监督候选人，并在获得教员职位、建立独立实验室和获得初始资金的过程中为候选人提供建议和支持。咨询委员会由Liston博士、Lee博士和Rajadhyaksha博士组成，他们对研究战略中概述的方法具有丰富的经验，将就研究的进行和解释以及在学术环境中探索早期研究的专业前景提供咨询。

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 intraneuronal 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.