# Stress plasticity of CRH neurons

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $410,979

## Abstract

Summary
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and altered circulating glucocorticoid levels are
closely associated with mental health disorders. Corticotropin-releasing hormone (CRH) neurons of the
hypothalamic paraventricular nucleus (PVN) control activation of the HPA axis, and direct stress- and anxiety-
associated behaviors. Alterations of the CRH neuron excitatory-inhibitory balance caused by plastic changes in
synaptic circuits result in altered HPA activity and shifting circulating glucocorticoids, which can lead to
changes in physiological homeostasis and behavioral outputs. Afferent noradrenergic circuits are critical for
controlling CRH neuron activity and HPA activation, yet little is known about the mechanism by which
norepinephrine (NE) regulates the CRH neurons or its plasticity with stress exposure. Our preliminary findings
reveal a novel mechanism of dendritic volume transmission in PVN CRH neurons that is activated by NE and
mediated by an astrocytic retrograde relay and gliotransmission to stimulate local excitatory synaptic circuits.
We have also found that stress-induced glucocorticoids cause a rapid suppression of the NE activation of the
PVN CRH neurons that is mediated by 1 adrenoreceptor desensitization. This rapid glucocorticoid effect is
likely to contribute to the feedback inhibition of the HPA axis, but its specificity to physiological vs.
psychological stress inputs and its role in stress-associated behaviors are not known. Here, we will use a
combination of patch clamp recordings, live-cell imaging, biochemical analysis, and behavioral testing to
address three specific aims. Aim 1 will focus on the pre- and postsynaptic mechanisms in CRH neurons in
brain slices that are responsible for 1 adrenoreceptor-induced neuronal-glial retrograde signaling that
activates upstream glutamate circuits. Aim 2 will determine the cellular mechanisms of the stress-induced
plasticity of the NE regulation of CRH neuron activity by probing the rapid glucocorticoid regulation of 1
adrenoreceptor trafficking and signaling. Aim 3 will take an in vivo approach to examine the role of the NE
afferents in HPA activation by physiological and psychological inputs, and to study the impact of the stress
plasticity of NE regulation of CRH neurons on a core stress behavioral phenotype, anxiety. Together, these
studies will fill an important gap in our understanding of the noradrenergic mechanisms of HPA regulation and
the stress plasticity of central circuits controlling the CRH neurons and their physiological and behavioral
outputs.

## Key facts

- **NIH application ID:** 10214477
- **Project number:** 5R01MH119283-03
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** JEFFREY G TASKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $410,979
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214477

## Citation

> US National Institutes of Health, RePORTER application 10214477, Stress plasticity of CRH neurons (5R01MH119283-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10214477. Licensed CC0.

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