# Decoding Neuropeptide S Modulation of Reward Seeking Behavior

> **NIH NIH F32** · UNIVERSITY OF WASHINGTON · 2022 · $72,082

## Abstract

Stress reduces an animal’s drive for seeking natural rewards but increases drug-seeking behavior. In humans,
anxiety disorders are also highly comorbid with substance-use disorder, and therefore a better understanding
of the underlying circuitry that connect these behaviors is necessary for the development of better treatment
strategies. Examining the role neuropeptide S (NPS), a neuropeptide shown to regulate anxiety-related behavior
through activation of the Gq-coupled protein receptor (NPSR1), plays in seeking social and natural rewards could
provide an interesting link between the body’s anxiety response with drug-seeking behaviors. The peri locus
coeruleus (periLC) produces NPS and sends projections to the orbitofrontal cortex (OFC), which contains dense
expression of NPSR1. Using a combination of retrograde tracing paired with in situ hybridization, as well as
whole-cell patch clamp electrophysiology, I found that the OFCNPSR1 neurons receive input from the periLC, and
that periLCNPS neurons project to the OFC. Therefore, I hypothesize that periLCNPS neurons drive natural reward-
seeking behavior through activation of OFCNPSR1 neurons. In order to dissect the periLCNPS-OFCNPSR1 projection’s
role in reward-seeking behavior, during my training period, I will learn to conduct novel in vivo calcium imaging
of network and single-cell activity, neuropharmacological and molecular manipulations. The first aim of this
research proposal is to determine the endogenous neuronal activity of periLCNPS during natural reward-
seeking behaviors. Previous research indicates that LC phasic activity is associated with reward stimuli, using
fiber photometry, I will measure the endogenous soma and terminal network activity of the periLCNPS neurons
during reward-related behaviors such as classical conditioning and social interaction tasks. Aim 1 will establish
how periLCNPS neurons behave in vivo to neutral and appetitive stimuli. The second aim of this research proposal
will investigate whether periLCNPS-OFCNPSR1 projections are necessary and sufficient for the modulation
of natural reward-seeking. I plan to use two-photon calcium imaging in a behaving mouse to investigate
OFCNPSR1 single-cell activity during delivery of appetitive stimuli with and without periLC terminal activation using
an excitatory opsin expressed in periLC excitatory terminals in the OFC. Finally, I will examine the sufficiency
and necessity of the periLCNPS-OFCNPSR1 projection in reward-seeking behaviors. To examine the sufficiency, I
will utilize in vivo optogenetic strategies to photoactivate the periLC-NPS terminals in the OFC during classical
conditioning and social interaction tasks. To test the projection’s necessity, I will use a conditional, viral-based
Crispr-Cas9 system to inactivate Nps or Npsr1 genes in the region of interest. These mice will then undergo
classical conditioning and social interaction assays. Here we will test the hypothesis that periLCNPS neurons
enhance natura...

## Key facts

- **NIH application ID:** 10536518
- **Project number:** 1F32DA055480-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Kasey Shea Girven
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $72,082
- **Award type:** 1
- **Project period:** 2022-09-16 → 2024-09-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536518

## Citation

> US National Institutes of Health, RePORTER application 10536518, Decoding Neuropeptide S Modulation of Reward Seeking Behavior (1F32DA055480-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10536518. Licensed CC0.

---

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