NIH grant: Connectomic mapping of microcircuits underlying infant directed behavior (1R01HD121730-01)

retained text

NIH grant 1R01HD121730-01: Connectomic mapping of microcircuits underlying infant directed behavior
Institute: {'code': 'HD', 'abbreviation': 'NICHD', 'name': 'Eunice Kennedy Shriver National Institute of Child Health and Human Development', 'admin_org_id': '12500030', 'admin_funding_url': ''}. PI: Catherine  Dulac. Award: $670194.
Start: 2026-06-24T00:00:00.
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.

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