# Effects of early life stress on functional development of prefrontal-amygdala connectivity

> **NIH NIH K00** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $77,127

## Abstract

PROJECT SUMMARY
Early life stress (ELS) is associated with a significant increase in risk for developing stress-related pathology,
including depression, anxiety, and post-traumatic stress disorder (PTSD). However, the mechanisms by which
ELS increases the risk for pathologies is not well understood. To study the effects of ELS on postnatal
development we take advantage of a well characterized neuronal circuit, the auditory fear circuit. Here we
investigate the mechanisms by which early life stress (ELS) alters aversive learning in the developing mouse.
We hypothesize that early life stress is accelerating the developmental maturation of the basolateral amygdala
(BLA), but not the prelimbic (PL) subregion of the medial prefrontal cortex. In Aim 1, we demonstrate that early
life stress leads to suppression of fear expression during pre-adolescence (postnatal day 21). Our data suggests
that ELS accelerates differentiation of parvalbumin positive (PV+) interneurons in the BLA. These neurons could
be causing hypoactivation of the BLA, resulting in the observed decreased fear phenotype. Through optogenetic
inhibition of PV+ neuron in the BLA we were able to rescue the fear expression deficit in our ELS mice. In Aim
2, Experiments 2.1 and 2.2, anatomical and functional connectivity of PL to BLA and BLA to PL projections will
be assessed. Using retrograde tracer injections and in-vivo electrophysiology during early postnatal development
(approx. postnatal days 16-30) we will test how ELS alters this cortico-limbic connectivity. We expect ELS
animals to have accelerated anatomical and functional connectivity of BLA to PL projection, but delayed PL to
BLA. In Experiment 2.3, we attempt to induce decreased fear expression in unstressed mice through acceleration
of PV+ maturation in BLA. Furthermore, we attempt to recover fear expression in stressed mice through a
pharmacologically induced acceleration of PL to BLA connectivity. In Aim 3, we delineate plans for postdoctoral
research, including the identification of a postdoctoral fellowship mentor and institution, and the use of calcium-
imaging to tract neuronal ensembles during a behavioral assay. During the K00 phase the applicant proposes to
acquire the remaining writing, presenting, networking and career skills necessary for a successful transition to
an independent researcher. Through the Research and Training Plan, the applicant will deepen her theoretical
and conceptual knowledge of developmental, cognitive and neural mechanisms underlying learning and
behavior, while acquiring advanced system level techniques, including in-vivo electrophysiology, calcium-
imaging, as well as perfecting coding and data analysis. The training acquired through this grant will allow the
applicant to use a multilevel approach when addressing developmental questions within the applicant's future
lab. Overall the work proposed will add a wealth of knowledge regarding the mechanisms by which early life
experiences lead to d...

## Key facts

- **NIH application ID:** 10328237
- **Project number:** 5K00MH124183-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Gabriela Manzano Nieves
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $77,127
- **Award type:** 5
- **Project period:** 2020-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328237

## Citation

> US National Institutes of Health, RePORTER application 10328237, Effects of early life stress on functional development of prefrontal-amygdala connectivity (5K00MH124183-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10328237. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*