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 Garca 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.
NIH ExPorter
NIH ExPorter