# Feeding regulation by cortical-amygdala circuits

> **NIH NIH R03** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $133,125

## Abstract

Project Summary
Obesity is currently affecting nearly 40% of adults in the U.S. and clearly a major health
problem. Energy intake exceeding the homeostatic need is an essential component for the
development of obesity. While the hypothalamus plays a key role in regulating energy
homeostasis, brain imaging studies in humans consistently found neural activities in the
extrahypothalamic region being highly correlated with the consumption of energy-dense food
and obesity. The most profound associations are located in reward- or salience-related brain
structures. It is therefore imperative to understand how these higher brain regions contribute to
the homeostatic regulation of food intake.
Our long-term goal is to understand how higher cortical structures exert top-down control of food
intake and homeostatic regulation. During the K01 period, enabled by whole-brain CLARITY
and lightsheet imaging, we conducted multiple brain-wide screenings to search for
extrahypothalamic circuits recruited by fasting. A previously uncharacterized posterior insular
cortex to basolateral amygdala projection (pINS-BLA) was unbiasedly identified as one of the
most active projections recruited by overnight fasting based on immediate early gene
expression. The insular cortex, a key site for integrating internal and external sensory
information and encoding valances, is also one of the most prominent brain regions found to be
associated with food reward and obesity across numerous human imaging studies. In this
proposal, we will test the hypothesis that the activity of this novel pINS-BLA projection encodes
top-down hunger signal and therefore positively regulates food intake. We will pursue the
following two specific aims: (1) Employ fiber photometry to track and quantify circuit dynamics of
the pINS-BLA projection in relation to fasting and re-feeding. (2) Use optogenetics to determine
the causal significance of the pINS-BLA projection in food consumption.
The studies proposed here will build upon the unique brain-wide screening capacity and the
original discovery of an insular cortex to amygdala projection, both achieved during the K01, to
unmask a new top-down mechanism of feeding regulation. The completion of this proposal will
greatly expand the existing hypothalamic-centered understanding of homeostatic control. This
knowledge will provide insight into how higher brain functions are altered during obesity and
offer a novel perspective of targeting obesity, both of which will lay the groundwork for our
subsequent R01 application.

## Key facts

- **NIH application ID:** 10136596
- **Project number:** 5R03DK124731-02
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Li Ye
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $133,125
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136596

## Citation

> US National Institutes of Health, RePORTER application 10136596, Feeding regulation by cortical-amygdala circuits (5R03DK124731-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10136596. Licensed CC0.

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