# Fragmented early-life experiences, aberrant circuit maturation, emotional vulnerabilities

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $473,431

## Abstract

The overall Center will integrate a multidisciplinary group of scientists to investigate the developmental origins
of vulnerability to mental illness, with a focus on perturbed environmental / sensory signals impacting brain
circuits during sensitive developmental periods. Guided by the constructive suggestions of the Reviewers,
Project 1 will exploit rat and mouse systems to directly test our overarching hypothesis that fragmented
and unpredictable early-life sensory signals (FRAG) promote functional deficits in pleasure and
reward-seeking behaviors by disrupting normal maturation of the underlying brain circuits.
 The studies using experimental animals will enable addressing the hypothesis at molecular, cellular
and circuit levels of analysis that are not possible in humans. Coupled with the use of structural and
functional neuroimaging approaches, our experimental studies will overlap and integrate with human subject
studies aimed at modeling network trajectories, allowing inferences of processes and mechanisms across
species. Synergizing with Projects 2-4 and the Imaging and BCDM cores, Project 1 defines trajectories
considering sex-dependent differences, truly bridging across species. Importantly, rodent experiments
enable direct testing of causality of correlative observations made across species and provide mechanistic
insight via intervention studies that target candidate mechanisms. These approaches further capitalize on
species-unique opportunities including short life span, access to brain tissue and controlled interventions,
utilizing the latest Neuroscience techniques.
The goals of Project 1 are: (a) To test the hypothesis that aberrant maturation of pleasure and reward circuits
underlies FRAG-evoked anhedonia, using state-of-the-art structural and functional (resting state fMRI) imaging
and mechanistic interventions; (b) Test the hypothesis that aberrant function of pleasure and reward circuits is
a mechanism for FRAG-evoked anhedonia, using cutting-edge viral-genetic technologies; (c) Test if early-life
FRAG creates ‘epigenetic signatures’ using novel within subject analyses, and if these provide predictive
markers for emotional vulnerabilities in children.

## Key facts

- **NIH application ID:** 9939734
- **Project number:** 5P50MH096889-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Tallie Z. Baram
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $473,431
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939734

## Citation

> US National Institutes of Health, RePORTER application 9939734, Fragmented early-life experiences, aberrant circuit maturation, emotional vulnerabilities (5P50MH096889-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9939734. Licensed CC0.

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