Maturation of somatosensory circuits for social behaviors

触摸有力地促进了亲子互动，这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，触觉在整个发育过程和成年生活中继续在沟通和社会互动中发挥关键作用。触觉感知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。虽然触觉感觉加工和社会行为之间的关系已经从临床角度用心理物理范式进行了广泛的研究，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知之甚少。了解社会特征是如何与早期触觉感官输入一起编码的，将为整合初级感官处理和高阶认知特征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（一种在广泛的社会行为中至关重要的神经肽）如何调节浅表神经元内回路以促进社会接触的发展。我们选择关注涉及L1 - rein表达（L1 - Re）中间神经元的回路，因为它们在出生后早期的感觉输入过程中具有独特的连接和限制锥体神经元激活的功能。在目的1中，我们将调查桶状皮质浅层中表达催产素受体（OXTRs）的神经元类型，并确定催产素在L1 Re中间神经元调节回路中的功能。在Aim 2中，我们将检查大坝诱导的社交接触期间新生小鼠幼崽的体内神经元活动，并确定L1 Re中间神经元中催产素信号的中断如何影响这种活动。在Aim 3中，我们将通过纵向双光子成像来扩展我们对催产素在社交接触出现中的作用的研究，以涵盖从新生儿阶段到成年的整个发育时期，并在这段时间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，可以帮助改进治疗ASD症状以及其他神经发育障碍的治疗方向。通过解决这些问题并开展建议的工作，候选人将建立技术和专业技能，为未来作为独立研究人员的职业生涯奠定坚实的基础。共同导师，博士。De Marco García和Froemke将通过定期会议（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，并在确保教师职位，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。咨询委员会由博士组成。Liston， Lee和Rajadhyaksha在研究战略中概述的方法方面拥有丰富的经验，他们将为研究的实施和解释以及在学术环境中引导早期研究的专业景观提供咨询。

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.