# Epigenetic Mechanisms Regulate the Development of Parental Behavior

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $318,023

## Abstract

PROJECT SUMMARY
It is widely reported that neglected children become neglectful parents. This cycle of child maltreatment is
responsible for a large proportion of child abuse and neglect in the United States. Presently there are no rodent
models that directly investigate how dysregulation of the maternal brain mediates neglect or how the early
experience of neglect is transmitted across generations. The overall objective of this proposal is to develop a
clinically relevant mouse model to identify molecular mechanisms of infant neglect that can be targeted to
reverse the cycle of pathological parenting. The medial preoptic area of the hypothalamus (MPOA) coordinates
parental behavior by inhibiting neural pathways involved in infant avoidance and activating pathways involved
in approach. Hormonal stimulation associated with late pregnancy and birth is one factor that determines which
pathway infant stimuli will activate in mother rats. Mother-infant interaction at birth, in the context of hormonal
exposure, induces plasticity in the approach pathway that supports the continuation of mothering behavior. Our
central hypothesis is that plasticity in the maternal neural circuit is regulated by experience-driven chromatin
modifications. Chromatin is the complex of DNA compactly coiled around histone proteins. The post-
translational modifications of histones by histone acetyltransferase (HAT) enzymes leave “epigenetic marks"
that exist above the level of the genome and control gene expression. Our preliminary data indicate that the
HAT activities of the chromatin-modifying enzyme CREB binding protein (CBP) critically mediate plasticity in
the maternal neural circuit. Aim 1 will determine the extent to which conditional mutation of CBP-HAT causes
maternal neglect and whether wildtype female offspring that experience early life neglect become neglectful
mothers in adulthood. Aim 2 will determine the extent to which the behavioral transmission of neglect from
mother-to-daughter is linked to dysfunction in CBP-HAT in the maternal neural circuit in response to infant
stimuli at birth and Aim 3 will identify the critical developmental time point when the maternal neural circuit is
programmed for neglect/care. To determine the epigenetic program that mediates the behavioral transmission
of neglect, we propose a highly innovative method in which neurons that are activated (fire action potentials)
during particular experiences become “Tagged” with a green fluorescent protein (GFP) that is used to isolate
these cells for downstream molecular analyses. Aim 4 will use this technique to examine the downstream
molecular pathways that mediate the transmission of neglect in select neurons that are activated during the
early life experience of neglect or neurons that are activated during the adult onset of neglect. Importantly, the
cycle of child maltreatment cannot be broken without an understanding of the neurobiological mechanisms that
mediate and perpetuate neglect....

## Key facts

- **NIH application ID:** 9961388
- **Project number:** 5R01HD087709-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Danielle Suzanne Stolzenberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $318,023
- **Award type:** 5
- **Project period:** 2016-08-25 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961388

## Citation

> US National Institutes of Health, RePORTER application 9961388, Epigenetic Mechanisms Regulate the Development of Parental Behavior (5R01HD087709-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9961388. Licensed CC0.

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