# Neural Pathway Linking Nutritional State To Food-Cue Responses In Insular Cortex

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $432,500

## Abstract

Project Summary/Abstract
Hunger is typically elicited by negative energy balance, and causes a state of increased motivation to seek out,
work for, and eat food. Hunger biases attention toward food-associated cues (e.g. candy bar wrappers) so that
calorie-dense foods can be found and consumed in order to restore energy balance. Enhanced behavioral
sensitivity to food cues remains a major obstacle to weight-loss programs involving food restriction, and can
even persist in satiated individuals suffering from obesity or eating disorders. Despite the clinical importance of
this phenomenon, the cellular and circuit mechanisms by which hunger biases cognitive processing towards
food-predicting cues remain largely unknown. A key brain area known to integrate information about internal
bodily states such as hunger with external sensory cues to drive goal-directed behavior is the insular cortex
(IC). Neuroimaging studies in humans have consistently found that hunger-dependent increases in the
incentive value of visual food cues correlates with increased food-cue-evoked responses in IC. In rodents, an
intact IC is critical for learned food-predicting cues to induce food-seeking behavior, potentially due to its role in
the retrieval of the incentive value of these cues. The overarching goal of this proposal is to define the neural
pathways by which hunger selectively enhances responses to food cues in IC. One promising starting point for
this pathway is the set of hypothalamic agouti-related protein (AgRP) neurons that integrates interoceptive
signals of negative energy balance. Hunger-related behaviors are restored in sated mice by activation of these
neurons. Moreover, hunger-related enhancement of food-cue responses in IC are restored in sated human
subjects by systemic injection of ghrelin, a hunger-stimulating hormone that activates AgRP neurons. We will
combine reversible manipulation of AgRP neuron activity with a new imaging approach we developed for long-
term imaging of the activity of individual neurons in mouse IC across slowly-changing motivational states. In
Aim 1, we will test whether visual food cue responses in specific subsets of IC neurons are (i) selectively
enhanced by food restriction, (ii) strongly attenuated by satiety, and (iii) restored by chemogenetic activation of
AgRP neurons. In Aim 2, we will determine whether basolateral amygdala axons in IC (BLAàIC) are a
necessary source of hunger-dependent food-cue information, via long-term imaging and optogenetic silencing
of BLAàIC axons. In Aim 3, we will test the hypothesis that AgRP neurons projecting to the paraventricular
thalamus (AgRPàPVT) mediate hunger-dependent modulation of food-cue responses in IC by inhibiting PVT
inputs to BLA, using innovative circuit mapping techniques in brain slices and in vivo, together with optogenetic
stimulation and silencing of AgRPàPVT neurons. This work should greatly advance our understanding of the
mechanisms by which hunger exerts its pot...

## Key facts

- **NIH application ID:** 9975003
- **Project number:** 5R01DK109930-05
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Mark L Andermann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,500
- **Award type:** 5
- **Project period:** 2016-07-19 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975003

## Citation

> US National Institutes of Health, RePORTER application 9975003, Neural Pathway Linking Nutritional State To Food-Cue Responses In Insular Cortex (5R01DK109930-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9975003. Licensed CC0.

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