# Neural mechanisms of taste and metabolic state integration in the brainstem

> **NIH NIH R34** · CORNELL UNIVERSITY · 2022 · $718,725

## Abstract

ABSTRACT
The taste of food is a critical factor that determines whether an organism will accept or reject a food source. In
addition, the sensory perception of food taste changes significantly depending on the metabolic state of animals.
Despite the significant progress in understanding the homeostatic biology of food intake in the mammalian brain,
how metabolic states (e.g., how hungry an animal is) alter the perception of food taste at the level of specific
neuronal circuits remains poorly understood. Here, we assembled a team of investigators that will use
quantitative measurements of behavior, cutting edge 3P microendoscopy, and optogenetic manipulation of
neural activity to study how taste representations in the brainstem are modulated with metabolic state, and how
the state dependent activity of brainstem taste circuits contributes to the regulation of ingestive behaviors in
mice. Specifically, this new team of investigators will probe the functions and the state dependent activity of two
distinct populations of neurons, sugar sensitive calbindin 2- neurons (Calb2) and bitter sensitive somatostatin-
neurons (Sst), in the rostral nucleus solitary tract (rNTS), the first central relay station of the taste pathway. In
Aim 1 the investigators will develop and optimize a state of the art 3-photon (3P) microendoscope that will allow
optical access to Calb2 and Sst neurons in the rNTS at cellular resolution. In Aim 2, the 3P microendoscope will
be used to examine the taste responses of Calb2 and Sst neurons in hungry and sated mice to investigate
whether sugar or bitter responses are modulated in response to changes in metabolic state. In Aim 3, the
investigators will investigate whether acute changes in the hunger state of mice affect the taste representations
in the rNTS by artificially modulating the activity of hunger promoting AgRP neurons in the hypothalamus. More
specifically, they will record the activity of Calb2 or Sst neurons using the 3P microendoscope, while
optogenetically activating or inhibiting AgRP neurons of sated or hungry mice that are offered a sugar solution
or sugar plus bitter mixture. The proposed study will provide critical information for understanding a core
mechanism of taste and metabolic state integration in the brainstem. It will also allow the team to investigate
whether taste coding is modulated in the brainstem based on metabolic state before the information is sent to
higher-order gustatory nuclei and to the insula cortex in a feed-forward fashion. Together, the proposed
experiments will generate novel knowledge and provide necessary technical and conceptual advances to lay the
groundwork for a subsequent Targeted BRAIN Circuits R01 with the same team of investigators aiming to further
investigate how brainstem taste circuits communicate with other central gustatory nuclei in a metabolic state
dependent manner to control ingestive behaviors in mice.

## Key facts

- **NIH application ID:** 10524319
- **Project number:** 1R34NS128872-01
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Nilay Yapici
- **Activity code:** R34 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $718,725
- **Award type:** 1
- **Project period:** 2022-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10524319

## Citation

> US National Institutes of Health, RePORTER application 10524319, Neural mechanisms of taste and metabolic state integration in the brainstem (1R34NS128872-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10524319. Licensed CC0.

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