# Determining the unique and dynamic neural constellation belonging to acute and chronic stress states

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $492,357

## Abstract

Project Summary: The objective of this “Biobehavioral Research Awards for Innovative New Scientists”
proposal is to determine the contributions of the CRF (corticotropin releasing factor) system to encoding and
responding to salient stimuli in the environment in individuals with different life histories of stressor exposure.
CRF is a neuropeptide neuromodulator that is expressed in several brain regions and is released in response to
both positive and negative arousing environmental stimuli. It is unclear how CRF as a brain wide neural system
differentially responds to stimuli with different valences to motivate appropriate approach or avoidance behaviors.
In addition, there is evidence that the CRF system is highly plastic and can undergo allostatic adaptations in
response to stressor exposure. Moreover, it is thought that in pathological states of allostatic overload, these
adaptations in the CRF system persist in suboptimal ways. Yet, it is unclear how the activity patterns of CRF
enriched nuclei across the brain are altered in a stress-induced state of allostatic overload, nor is it understood
how changes at different CRF loci combine to promote maladaptive behavioral responses. This proposal seeks
to resolve these unanswered questions by testing the hypothesis that positive or negative salient environmental
stimuli stimulate the activity of unique ensembles of CRF-containing nuclei to drive the appropriate affective
behavioral responses. Furthermore, that chronic stress shifts CRF network responsivity toward greater activation
to negative stimuli and depressed activation toward positive stimuli which leads to enhanced avoidance of these
salient environment stimuli. To test this hypothesis, I propose two specific aims.
Aim 1. Generate a whole brain functional map of activity patterns of CRF-containing neurons in response
to acute environmental stimuli in control and chronically stressed male and female mice. This aim uses
three-dimensional functional neuroanatomy and in vivo calcium imaging techniques to determine the activity
patterns of CRF expressing nuclei in response to salient environmental stimuli that carry different valences. We
will assess this in control and chronically stressed male and female mice. Collectively, these experiments will
offer a holistic perspective on the response(s) of CRF to salient stimuli by viewing it as a whole-brain neural
system rather than focusing on a single region or pathway.
Aim 2. Determine the effects of site-specific suppression of CRF-containing neurons or deletion of CRF
peptide on behavioral responses to acute salient stimuli presented to control and stress-exposed mice.
This aim assesses the relative contributions of CRF localized to different brain nuclei in modulating approach
and avoidance behavior by utilizing cutting-edge transgenic and optogenetic techniques.
The purpose of the BRAINS program is to nurture innovative new investigators by promoting investigation of
ambitious and important q...

## Key facts

- **NIH application ID:** 10147778
- **Project number:** 5R01MH122749-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Julia C Lemos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $492,357
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147778

## Citation

> US National Institutes of Health, RePORTER application 10147778, Determining the unique and dynamic neural constellation belonging to acute and chronic stress states (5R01MH122749-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10147778. Licensed CC0.

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