# Central regulation of sodium appetite via synergistic action of RAAS-sensitive neurons

> **NIH NIH K99** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $166,104

## Abstract

PROJECT SUMMARY
The motivation to consume sodium, often referred to as "sodium (or salt) appetite", is a hard-wired neural
response to sodium deficiency regulated by the Renin-Angiotensin-Aldosterone System (RAAS). Impaired
function of this system results in inappropriate sodium ingestion that can have deleterious effects on
cardiovascular health. The studies and career development activities in this K99/R00 proposal are designed to
provide the candidate, Dr. Jon Resch, with the training necessary to become an independent investigator with
a research program examining the neural control of sodium appetite. Recently two RAAS-sensitive neuronal
populations have been shown to regulate sodium appetite: aldosterone-sensing neurons in the nucleus of the
solitary tract (NTSHsd11b2 neurons) and a subpopulation of angiotensin II (AngII)-sensing neurons in the
subfornical organ (SFO). Importantly, both NTSHsd11b2 neurons and AngII-sensing SFO neurons are necessary
for deficiency-induced sodium appetite, and NTSHsd11b2 neurons require concurrent AngII signaling to drive
rapid and robust sodium consumption. Furthermore, both RAAS-sensitive populations promote sodium
ingestion via projections to the ventral lateral bed nucleus of the stria terminalis (vlBNST). This strongly
suggests that the vlBNST is the critical site where neural processing occurs to coordinate sodium appetite.
However, the functional complexity and neurochemical heterogeneity of the vlBNST poses a significant
challenge to finding and investigating the neurons within it that regulate sodium appetite. In order to elucidate
the neural circuits that control sodium appetite, the proposed research will (1) confirm the site of AngII
signaling that enables NTSHsd11b2 neurons to drive sodium appetite, (2) decipher the wiring diagram of RAAS-
sensitive inputs to the vlBNST, (3) use high-throughput single-cell transcriptomics to generate a "molecular
census" of vlBNST neurons, and (4) identify the molecular signature of vlBNST "sodium appetite" neurons.
The results of these experiments will form the foundation for many future studies regarding sodium appetite
control by the BNST and the downstream circuits through which these neurons produce the motivation to
consume sodium. The proposed research and training will be conducted within the Endocrine Division of the
Department of Medicine at Beth Israel Deaconess Medical Center, and will ensure the Dr. Resch's successful
transition to scientific independence. Dr. Resch will receive training in CRISPR/Cas9-based methods for
mouse genetic engineering from his primary mentor, Dr. Bradford Lowell, and in single-cell transcriptomics
from his advisory committee members, Drs. Evan Rosen and Linus Tsai. Furthermore, through acquiring the
aforementioned technical expertise, coursework, attendance of scientific meetings, and lab management
training from his primary mentor during the initial K99 award period, Dr. Resch will cultivate an independent
research progra...

## Key facts

- **NIH application ID:** 9853841
- **Project number:** 5K99HL144923-02
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Jon Resch
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $166,104
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853841

## Citation

> US National Institutes of Health, RePORTER application 9853841, Central regulation of sodium appetite via synergistic action of RAAS-sensitive neurons (5K99HL144923-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853841. Licensed CC0.

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