# Synapse to behavior, interrogating pathways underlying the control of food intake

> **NIH NIH F99** · WASHINGTON STATE UNIVERSITY · 2024 · $41,352

## Abstract

PROJECT SUMMARY
More than 40% of adults in the United States are obese, and that number is expected to rise to over 50% by
2030. Obesity is a critical health concern as it is associated with several leading causes of death including
diabetes, heart disease, stroke, and cancer. Ingestion of a meal can elicit both positive and negative feelings.
However, the pathways underling these different valences are not well understood, but maladaptive changes
could have broad implications for both overeating and emotional disorders. Drugs that inhibit food intake (FI)
also often lead to aversive side-effects like nausea. Understanding what mediates the positive or negative
feelings associated with satiety is therefore critical to help drive the development of treatments for obesity without
aversive side-effects. Recent work has identified a population of cholecystokinin (CCK) expressing neurons in
the nucleus of the solitary tract (NTS). Stimulation of these neurons leads to a decrease in FI, but stimulation of
terminals in the paraventricular hypothalamus (PVH) is rewarding, while stimulation of terminals in the
parabrachial nucleus (PBN) is aversive. However, it remains unclear what drives these divergent projections
physiologically and how terminals activate neurons in the PVH and PBN. To investigate this, I first characterized
what types of vagal afferents innervate NTS-CCK neurons and what currents they express. My results suggest
that there are two subpopulations of neurons: one that is downstream of both CCK and serotonin (5-HT) sensitive
afferents and another that is downstream of only CCK sensitive afferents. Information carried by 5-HT sensitive
afferents is thought to be aversive, while information carried by CCK sensitive afferents is thought to be
rewarding. Thus, I hypothesize that NTS-CCK neurons projecting to the PVH are driven primarily by CCK
sensitive afferents, while PBN projecting neurons receive inputs from both CCK and 5-HT sensitive afferents.
Further, I posit that release of fast transmitters and peptides will have different effects on downstream cells in
the PVH and PBN. These studies will provide valuable information regarding the cellular mechanisms underlying
previously reported behavioral findings. They will also help guide future studies aiming to develop more selective
and less aversive therapies for the treatment and prevention of obesity. To accomplish the proposed experiments
in the F99 phase, I will need to learn stereotaxic injections as well as in-slice photostimulation techniques. My
sponsor, Dr. Suzy Appleyard, and co-sponsor, Dr. Shane Hentges, have expertise in all proposed techniques as
well as established mentoring records. During the K00 phase, I plan to build on the skills learned during the F99
phase by identifying a supportive and knowledgeable postdoctoral mentor. Specifically, I will receive training on
in-vivo opto and chemogenetic stimulation, in-vivo neuronal recording techniques, and computational models ...

## Key facts

- **NIH application ID:** 11001682
- **Project number:** 1F99NS135809-01A1
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Eric Thomas Winzenried
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,352
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11001682

## Citation

> US National Institutes of Health, RePORTER application 11001682, Synapse to behavior, interrogating pathways underlying the control of food intake (1F99NS135809-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11001682. Licensed CC0.

---

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