# Stress-induced impairments in endogenous neurosteroid signaling in the BLA negatively impacts network and behavioral states

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 2022 · $498,891

## Abstract

Project Summary
The episodic nature of psychiatric disorders suggests that the brain shifts between pathological and healthy
brain states. Fear and anxiety have been correlated with changes in oscillations between the medial prefrontal
cortex (mPFC) and basolateral amygdala (BLA) and abnormalities in these networks have been identified in
patients with a range of psychiatric disorders and we propose that these networks may impact emotional
processing more broadly. However, we understand very little about the mechanism(s) whereby networks shift
between states. 5α-reduced neurosteroids, including allopregnanolone, have been suggested to play a role in
affective switching and have been shown to exert robust anxiolytic and antidepressant effects in preclinical
models and in clinical trials. In fact, an allopregnanolone analog recently received FDA approval for the
treatment of postpartum depression. The current study builds on these findings to investigate the potential role
of endogenous neurosteroids in mediating transitions between healthy and unhealthy network and behavioral
states. Given that stress has been implicated in numerous psychiatric disorders, we propose to utilize a chronic
unpredictable stress (CUS) model to evaluate the impact on mPFC-BLA network function. We propose that
stress disrupts network function by impairing local neurosteroid signaling in the BLA (supported by preliminary
data) and that increasing the capacity for endogenous neurosteroidogenesis can restore healthy network
function. Our proposed mechanism involves the action of neurosteroids on GABAAR δ subunit-containing
receptors, expressed at a high density in parvalbumin (PV)-positive neurons in the BLA, which are known to
modulate oscillations within and between the mPFC-BLA. Thus, this application will test the hypothesis that
deficits in endogenous 5α-reduced neurosteroid signaling in the BLA, via δ-subunit containing GABAARs on PV
interneurons, contribute to the stress-induced impairments in network and behavioral states.

## Key facts

- **NIH application ID:** 10491237
- **Project number:** 5R01MH128235-02
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Jamie Lynn Maguire
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $498,891
- **Award type:** 5
- **Project period:** 2021-09-20 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491237

## Citation

> US National Institutes of Health, RePORTER application 10491237, Stress-induced impairments in endogenous neurosteroid signaling in the BLA negatively impacts network and behavioral states (5R01MH128235-02). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10491237. Licensed CC0.

---

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