# Neural circuits underlying thirst and satiety regulation

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2020 · $385,250

## Abstract

Project Summary
A forebrain structure, lamina terminalis (LT), plays a key role in both sensing internal water balance and
regulating thirst through its downstream neural circuits. Recent studies have identified genetically-defined
neural populations and circuit organization that control the initiation of drinking. The activity of these thirst
neurons are rapidly suppressed with the onset of water consumption prior to absorption of ingested water.
These results suggest that the LT integrates the homeostatic need and real-time satiety signals to optimize
drinking. However, little is known about the functional significance of such integration and the underlying neural
circuits. These studies have been hindered by the anatomical complexity of the LT and the lack of genetic
handle on related neural circuits. Recent technological advances in transcriptomic analysis and neural
manipulation/mapping tools have opened up an exciting window to study neural circuit at cell-type-specific
precision. The present study combines such advanced approaches to delineate the cellular organization of the
LT and the neural circuitry underlying rapid thirst satiety. These studies build on our results that thirst neurons
in the subfornical organ (SFO) receive multiple satiety signals through anatomically and temporally separable
neural substrates. In Aim 1, we will employ high-throughput single-cell RNA-seq analysis to elucidate a
transcriptomic atlas of individual nuclei of the LT. This study will provide a framework to link individual
physiological functions of the LT with molecularly-defined cell types. Based on our results, we will examine
whether thirst neurons comprise functionally distinct multiple subpopulations in the LT. In Aim 2, we will
characterize two temporally distinct satiety signals in the SFO induced by drinking action and osmolality
change by water intake. We will determine the signaling pathways that carry individual thirst satiety signals
using intragustric fluid infusion and in vivo optical recording from the SFO in awake-behaving animals. In Aim
3, we will define the neural substrates and circuits that mediate osmolality-induced satiety by retrograde viral
tracing and electrophysiological tools. Once we identify candidate brain areas, we will apply an innovative
“monosynaptic” scRNA-seq analysis to identify specific genes enriched in the neurons that transmit the
osmolality signal to the SFO. The outcome of this project will advance our understanding of neural basis of
thirst and satiety regulation.

## Key facts

- **NIH application ID:** 9998043
- **Project number:** 5R01NS109997-03
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Yuki Oka
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,250
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998043

## Citation

> US National Institutes of Health, RePORTER application 9998043, Neural circuits underlying thirst and satiety regulation (5R01NS109997-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9998043. Licensed CC0.

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