Tactile modulation of the neonatal hypothalamus

PROJECT SUMMARY- Social touch contributes to brain and behavior development in the infant attachment sensitive period. The long-term goal of this project is to understand the sensitive period neural mechanisms of social touch. We do not yet understand the precise mechanisms by which social touch in infancy is encoded in the brain. This proposal will help address this need. Oxytocin (OXT) is a candidate touch encoding factor because of its roles in infant and adult social behavior. Receptors for OXT (OXTR) are expressed in the developing brain in touch circuits, as well as in a subset of peripheral sensory neurons. Sensory experience increases infant OXT production in the paraventricular nucleus (PVN) and social touch increases the release of OXT. Pre-weaning OXTR KO mice have blunted OXT production and blunted PVN activity. Mice with OXTR deletion from peripheral sensory neurons have impaired social behavior and increased aggression as adults. These data are consistent with a hypothesis that OXTR on peripheral sensory neurons enhances the touch- dependent development of the PVN OXT system with lifelong implications for species-typical social behavior. The experiments in this proposal will test the novel hypothesis that OXTR on peripheral sensory neurons refine the PVN through social touch dependent activity. Using bulk and cell-type specific transcriptomics and circuit- based activity, we will determine the role that peripheral sensory OXTR activity has on the development of the hypothalamus. All of the proposed experiments will be performed in infant mice and the potential for sex differences will be explicitly tested. Even if our organizing hypothesis is not supported, the data generated will add new knowledge regarding the impact of touch on hypothalamus development in this sensitive period. The knowledge gained by these experiments will be informative to improve prevention and intervention during experience-dependent infant attachment.