# The cellular memory of early life adversity

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $522,572

## Abstract

Abstract
Gestational and early postnatal adverse experiences, because of their psychopathological consequences later in
life, represent a significant burden for the affected individual and society. We identified an epigenetic motif at
two thousand genomic regions in neurons that, via dynamic switching between methylated and unmethylated
states, may control gene expression. The stochastic balance between the two states is altered by early life
adversity in a subpopulation of neurons, resulting in abnormal neuronal functioning. We will test the
hypothesis that permanent changes in the methylation state of key “switches” in the adversity-activated
neurons represent the “cellular memory” of early life adverse experiences. Adversity-induced epigenetic
changes increase the excitability of neurons, making them permanently eligible for recruitment during
behavioral tasks. This in turn, increases the responsiveness of the circuit to novel/stressful stimuli, manifested
as exaggerated fear reaction/anxiety later in life. Besides of the theoretical implications (coding environmental
effects via binary epigenetic switches), our work has translational significance. The sensitivity of DNA
methylation based switches (due to their metastability), compared to the rest of the epigenetically more stable
genome, provides an opportunity for their selective manipulation to mitigate the adverse effects of ELA.

## Key facts

- **NIH application ID:** 10338187
- **Project number:** 5R01MH117004-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Miklos Toth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $522,572
- **Award type:** 5
- **Project period:** 2020-03-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10338187

## Citation

> US National Institutes of Health, RePORTER application 10338187, The cellular memory of early life adversity (5R01MH117004-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10338187. Licensed CC0.

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