# Maternal Influence Over Prefrontal Cortex and Transition to Independence - Revision - 2

> **NIH NIH R37** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $130,908

## Abstract

Abstract
 Infant attachment occurs in species that require parental care for survival, such as children and rodents,
and permits the use of animal models to explore mechanisms for both attachment and attachment dysfunction.
Here we propose to use infant rats to understand the brain mechanisms for the attachment figure to reduce fear
in the infant (i.e. parent functioning as a safe base). Using an approach involving behavior and brain assessment
at the network level (communication between brain areas), circuit level (specific set of neurons) and molecular
level (events within neurons) to ask, what is different during learning about a threat when the infant is alone or
with the mother? How does the infant’s brain lose the ability to use the mother as a safe base with age or
pathology? Since clinical literature shows the parent has limited functions as a safe base when the infant
experiences rough treatment from the parent, we ask how is it possible for the brain to lose processing of the
parent as a safe base?
 To address these questions, we use odor-shock fear conditioning because it is a robust neurobehavioral
system across children and infant rats, has proven translational value, and the neural network is well-defined.
The first five years of this award has shown that, during a sensitive period, maternal cues interface with the threat
learning circuit in at least two ways. First, the mother’s presence changes the infant’s network processing of
threat by adding in a node (brain area), the ventral tegmental area (VTA), which suppresses another node, the
basolateral amygdala (BLA) via dopamine release (DA). Second, the mother’s presence suppresses pups’
immature cascade of intracellular signaling molecules (e.g., ERK) critical for plasticity underlying learning and
memory. We expand this research on typical-rearing to infants that have experienced rough maternal care and
behaviorally show significant reduction in using the mother as a safe base. We ask how this adversity-reared
infant’s brain differs from the typically-reared infant within our behavior-to-neuron-to-molecule approach. In Aim
1 we describe the brain’s global network changes following adversity, while in Aim 2 we describe amygdala’s
BLA intracellular molecular cascade. In Aim 3, we focus on causation and chart the VTA-BLA neural circuit
using optogenetics to manipulate neurons with a laser light and electrophysiology to record neural activity. This
supplement builds on Aim 3 by using transgenic animals (genetic manipulation to permit laser light to
manipulate dopamine neurons) that allow direct and specific modulation of dopamine neurons to permit
us to precisely define the role of dopamine within the VTA-BLA circuit and used as a format to mentor a
postdoctoral fellow.
 The significance of this research is that it explores network and circuit development, asking how a brain
changes to accommodate behavioral transitions required during maturation. We use typical development, but
also ...

## Key facts

- **NIH application ID:** 10505206
- **Project number:** 3R37HD083217-08S1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** REGINA Marie SULLIVAN
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $130,908
- **Award type:** 3
- **Project period:** 2020-03-16 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10505206

## Citation

> US National Institutes of Health, RePORTER application 10505206, Maternal Influence Over Prefrontal Cortex and Transition to Independence - Revision - 2 (3R37HD083217-08S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10505206. Licensed CC0.

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