# Substance P-Mediated Enhancement of Salience for Cues Predicting Aversive Outcomes

> **NIH NIH R00** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2024 · $239,237

## Abstract

Project Summary 
Maladaptive fear exacerbates responses to aversive stimuli and enhances stress and anxiety. However, brain mechanisms that drive these aversive responses and enhance salience of aversive stimuli are not known. The excitatory peptide substance P produces a spatially restricted, glutamatergic long-term potentiation on a subset of Nucleus Accumbens core neurons that are known to promote aversion. Furthermore, this long-term potentiation occurs in the Nucleus Accumbens core following fear conditioning and can be suppressed by blocking substance P signaling. Glutamatergic inputs, particularly limbic inputs, to this sub-region are among several brain systems that encode salience to cues, suggesting substance P may drive integration of salience-related signals on these cells to promote learning about aversive stimuli that proceeds behavioral action. Using a multi-level approach including slice electrophysiology, optogenetics, and fiber photometry, this project aims to understand how substance P-mediated potentiation of saliencerelated inputs to the nucleus accumbens core promotes salience to cues predicting aversive outcomes and aims to develop brain stimulation paradigms to suppress fear responding.

## Key facts

- **NIH application ID:** 10839880
- **Project number:** 5R00MH123673-04
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Tanner Chase Francis
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $239,237
- **Award type:** 5
- **Project period:** 2022-07-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839880

## Citation

> US National Institutes of Health, RePORTER application 10839880, Substance P-Mediated Enhancement of Salience for Cues Predicting Aversive Outcomes (5R00MH123673-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10839880. Licensed CC0.

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