Connectomic mapping of microcircuits underlying infant directed behavior

About This Grant

PROJECT SUMMARY / ABSTRACT Parenting—a conserved caregiving behavior essential for offspring survival—is profoundly shaped by developmental and physiological states. While the hormonal regulation of parenting is well characterized, the circuit-level mechanisms that enable its flexible expression are poorly understood. Behavioral differences associated with developmental and physiological states likely involve coordinated synaptic remodeling across distributed brain circuits that are yet to be defined. Addressing this knowledge gap requires a high-resolution approach to map synaptic architecture across defined states. Our lab has identified POAGal⁺/Calcr⁺ neurons in the hypothalamic preoptic area as a central hub for parenting behavior. These neurons integrate diverse upstream inputs and project to distinct downstream targets, coordinating the hormonal, motivational, and motor components of caregiving. Prior work has shown that inputs to POAGal⁺/Calcr⁺ neurons originating from raphe nucleus serotonergic (5-HT) neurons and medial septum cholinergic (ACh) neurons exhibit state-dependent changes important for maternal behavior, suggesting dynamic circuit reorganization. This proposal aims to elucidate how synaptic inputs onto POAGal⁺/Calcr⁺ neurons are organized and remodeled across physiological and developmental transitions. We will employ volumetric correlated light and electron microscopy (vCLEM), genetic EM labeling, connectomics mapping, and machine learning-based morphological analysis to reconstruct complete synaptic input maps across states. These structural maps will be integrated with functional data and computational modeling to determine how synaptic changes modulate POAGal⁺/Calcr⁺ neuron activity. In Aim 1, we will define the synaptic input architecture in virgin females, classifying input types based on ultrastructural features. Aim 2 will compare synaptic inputs—particularly from 5-HT and ACh neurons—between virgin and postpartum animals to identify mechanisms of state-dependent remodeling. Aim 3 will investigate how these inputs are established and refined during development by analyzing synaptic organization at postnatal days 10 and 25, and modeling how these developmental changes shape neuronal activity and circuit function. Together, this work will uncover principles of how survival circuits adapt to internal state and developmental context through synaptic plasticity. Establishing a high-resolution framework for parenting circuit organization will provide a foundation for future studies of how early-life adversity or neuromodulatory dysfunction disrupts caregiving and offspring well-being.