Neural Mechanisms Linking Sensory Perception and Social Behavior

项目总结

PROJECT SUMMARY Abnormalities in sensory perception are prevalent features in individuals with autism spectrum disorders (ASD), accompanying the core social deficits. A central challenge in autism research is to identify alterations in neurobiological mechanisms that underlie processes as distinct as sensory perception and social cognition. As such, our long-term goal is to understand common developmental and circuit mechanisms shared by sensory and social information processing. Considerable evidence indicates that the neuropeptide oxytocin significantly contributes to a wide range of social behaviors, and more recently, it has been linked to synaptic plasticity in sensory cortices during development. These findings raise an exciting but untested possibility that oxytocin signaling is associated with both tactile processing and social function. In our preliminary studies, we found that oxytocin receptors (OXTRs) are expressed abundantly and specifically in the somatostatin-expressing interneurons (SST INs) in the primary somatosensory cortex (S1) during development. Activating OXTRs selectively and strongly depolarizes SST INs, while OXTR deletion in these neurons leads to hyperpolarization of the resting membrane potential and reduced in vivo network activity in the developing S1. In addition, mice with targeted OXTR deletion in SST INs show impaired texture discrimination and sensory sensitivity, as well as deficits in social preference. Based on these preliminary results, we hypothesize that oxytocin is required for establishing proper synaptic connectivity in the developing somatosensory cortex, and that impairment in oxytocin signaling leads to both tactile sensory abnormalities and social deficits. We will leverage our novel longitudinal 2-photon imaging technique, electrophysiological and genetic approaches to identify the cell-type specific role of oxytocin in the development of S1 and during acute social interactions through three aims. We will assess the effects of oxytocin on the growth and survival of SST INs, as well as the maturation of circuit connectivity in the developing S1 (Aim 1). We will dissect the role of oxytocin signaling in general tactile sensory processing, and in encoding social cues during social contacts (Aim 2). We will explore the behavioral outcomes of oxytocin signaling dysfunction and their neural corelates, and test if developmental tactile dysfunction as a result of OXTR deletion exacerbates social deficits (Aim 3). Together, the results are expected to reveal common neural mechanisms underlying sensory and social information processing, providing insights into basic rules for brain circuit development, as well as identifying early diagnostic markers associated with ASD and other mental disorders that can guide novel therapeutics.