Functional organization and plasticity of the oxytocin system for single or communal parenting in mice

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Project Summary (Project 1, Co-PIs: Froemke, Lin, Buzsaki) Oxytocin is a neuropeptide important for social behavior, such as maternal care, pair bonding, and cooperation by partners and groups. Direct axonal oxytocin release into various forebrain targets is critical for social behavior, but it remains unclear if the oxytocin system is heterogeneous and reflects important functional differences for certain cell subsets, relates to inter-animal differences in parental abilities, and if experience-dependent plasticity can adapt the oxytocin system to social and parental environments. Oxytocin administration might also be clinically promising for autism spectrum disorders, social anxiety, and post-partum conditions. However, it is imperative to understand what aspects of oxytocin release relate to parenting, cooperating, and communal living, and whether there are differences in oxytocin modulation that depend on sex, experience, or social context. Here we will address this critical knowledge gap. Recently, with the U19 Behavior Core we built a system for neural recordings and behavioral monitoring, continuously collecting data over days to months on home cage life as mice parent or co-parent together. This was combined with photo-tagged recordings in vivo of identified oxytocin neurons in maternal mice. Our documentary-style video recordings revealed previously-undescribed behavioral interactions by which experienced mothers seemed to encourage or perhaps ‘teach’ co-housed pup- naïve virgin females to engage in maternal care. These behaviors activated photo-tagged oxytocin cells in virgin PVN, providing a robust foundation for the current Project, in which our team aims to understand what aspects of maternal care- by single mothers, pairs, and small groups- activate oxytocin neurons, require oxytocin signaling, and might produce or depend on plasticity of this system upon transition to parenting. The central hypothesis is that the oxytocin system is attuned to social variables related to pup care and the behavior of other potential co-parents, to regulate the behavior of single and co-parents to assure pup survival. We further hypothesize that this depends on adult dominance interactions (studied with Project 2 and analyzed with the Computational Modeling Core) that set up social structures for effective co-parenting. We will monitor oxytocin neurons with in vivo and in vitro electrophysiology, photometry, and perform behavioral and opto-/chemo-genetic studies in adult mice to determine when and how oxytocin modulates neural circuits for social information processing and reliable maternal behavior, with mechanisms of modulation informed by Project 3 and relevant brain areas for social information processing identified in Projects 2 and 4. In Aim 1 we study initial plasticity of oxytocin cells when animals become single mothers, relating oxytocin cell firing to variables such nest building or pup temperature. In Aim 2, we ask if oxytocin neurons help experienced dams teach co-housed naive adults to co-parent. In Aim 3, we study groups of 3-4 mice (including an experienced dam and litter) to quantify dynamics of communal living and co-parenting, and how oxytocin helps ensure social network stability for raising infants.