# Molecular and Neural Mechanisms regulating Foraging and Food Intake

> **NIH NIH R35** · CORNELL UNIVERSITY · 2020 · $401,350

## Abstract

ABSTRACT
In normal individuals, food intake is strictly regulated by sensory, homeostatic and hedonic neural circuits, which
balance energy intake with energy expenditure. Failure to regulate food perception and appetite result in
maladaptive eating behaviors and an increase in the occurrence of metabolic syndromes and eating disorders.
Neural circuits that regulate food intake have been extensively investigated in rodent models. However, the
complexity of the mammalian brain makes it very challenging to explain the underlying molecular mechanisms
and circuit dynamics controlling food intake. I propose to use a genetically tractable model organism, the fly
(Drosophila melanogaster), to understand the fundamental principles of how the brain integrates the sensory
percept of food with the sensation of hunger to regulate food intake on the level of molecules, cells and circuits.
Flies are an excellent model to investigate these processes because they have 1000-fold fewer neurons in the
brain than mice, and yet they still show hunger states and specific food intake control remarkably similar to those
in vertebrates. Furthermore, the fly nervous system is more accessible for genetic modifications, anatomical
studies and monitoring the activity of large populations of neurons in behaving animals. Previously, I have shown
that flies, like humans, regulate their food intake by integrating the taste and nutrient value of food with hunger
sensation in the nervous system. I identified a novel class of excitatory interneurons (IN1) in the fly brain that
regulate food ingestion. In this project, we will first identify the IN1 food intake circuitry using optogenetics and
anterograde transsynaptic circuit tracing. Next, we will reveal how IN1 neurons and downstream circuitry change
activity during food search in a virtual reality foraging assay using two-photon microscopy. Finally, using cutting-
edge three-photon technology, we will capture the activity of IN1 neurons chronically in an intact fly as flies are
being food deprived. Functional dissection of IN1 circuitry will lead us to fundamental principles that the nervous
system uses to regulate food intake. In parallel with our food intake circuit dissection efforts, we also identified 8
evolutionary conserved genes in a large genetic screen for flies that fail to show compensatory feeding after 24
hours of food deprivation. We will anatomically and functionally dissect the role of these genes and the neural
circuits they control in regulating food intake. Finally, we will test the interaction of the candidate food intake
genes and the IN1 circuitry in regulating food perception and appetite control. Modelling the food intake and
appetite control systematically in a genetically tractable organism allows us to reveal new molecular and neural
control mechanisms. Once, we discover key mechanisms underlying food intake and appetite, we can search
for similar processes in more complex mammalian models and in pati...

## Key facts

- **NIH application ID:** 9990791
- **Project number:** 5R35GM133698-02
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Nilay Yapici
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $401,350
- **Award type:** 5
- **Project period:** 2019-08-07 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990791

## Citation

> US National Institutes of Health, RePORTER application 9990791, Molecular and Neural Mechanisms regulating Foraging and Food Intake (5R35GM133698-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9990791. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*