# Cellular substrates of early life trauma

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $586,450

## Abstract

Most psychiatric conditions have their highest incidence of onset in early life, and it is currently estimated that
one in five adolescents will develop such a condition that persists into adulthood. A major risk factor for such
disorders is the experience of childhood trauma. Among the brain regions most highly implicated in these
conditions is the medial prefrontal cortex (mPFC), which forms a synaptic network that plays important roles in
emotional regulation. During a developmental stage equivalent of human adolescence, rodents exhibit
heightened susceptibility to stress-induced behavioral phenotypes that resemble human conditions like anxiety
and depression, and that are accompanied by long-term changes in the structure and function of mPFC in
adulthood. However, it remains unclear whether unique mechanisms confer susceptibility to stress in immature
animals, or what processes immediately ensue upon exposure to stress in adults versus mice. The long-term
goal of this project is to reveal how trauma impacts directly on mPFC neurons, delineate substrates and
mechanisms in these effects, and understand the abnormal functional properties that result. In particular, our
preliminary data suggest that early adolescence is a sensitive period for noradrenaline-dependent suppression
of mPFC activity and excitability, and that engagement of this process during traumatic stress leads to a long-
lasting increase in threat avoidance, a potential correlate of human anxiety. We will make unprecedented use
of longitudinal calcium imaging in freely behaving mice to measure these physiological effects as well as
changes in mPFC activity that signal abnormal avoidance behaviors. Cellular and synaptic mechanisms for
hypoexcitability will be elucidated by electrophysiological recordings. Finally, we will use temporally specific
optogenetic manipulations to test whether recovering mPFC activity within specific projection pathways is
sufficient to reverse trauma-related phenotypes. We hope that be establishing this comprehensive paradigm of
stress susceptibility, we can shed light on biological factors that potentially contribute to a high rate of
childhood onset for psychiatric disorders.

## Key facts

- **NIH application ID:** 10100871
- **Project number:** 1R01MH124880-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Roger L Clem
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $586,450
- **Award type:** 1
- **Project period:** 2020-09-21 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10100871

## Citation

> US National Institutes of Health, RePORTER application 10100871, Cellular substrates of early life trauma (1R01MH124880-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10100871. Licensed CC0.

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