Molecular and Neural Mechanisms Regulating Foraging and Food Intake

Cornell University, Ithaca NY

Investigators

Linked publications & trials

Abstract

PROJECT SUMMARY Food intake is a finely tuned innate behavior controlled by a complex network of sensory, homeostatic, and hedonic mechanisms. In metabolic diseases such as obesity or eating disorders such as anorexia nervosa, the body's normal perception of food and appetite is altered, leading to overeating and weight gain or reduced appetite and weight loss. Understanding the genetic and neural mechanisms regulating food intake and appetite is essential for developing effective treatments for both conditions. While neural circuits that regulate food intake have been extensively studied in rodent models, the complexity of the mammalian brain makes it challenging to explain the underlying molecular mechanisms and circuit dynamics. The overarching goal of this project is to understand the neurogenetic mechanisms by which the brain communicates with the body to regulate food intake and foraging at the neural and molecular levels. We use a genetically tractable model organism, the fly, Drosophila melanogaster, to study the metabolic-state-dependent regulation of food intake and foraging at the levels of genes, cells, and circuits. Previously, we pioneered in vivo functional imaging methods to record the activity of molecularly defined populations of neurons in the fly brain and the enteric nervous system during food ingestion. We also developed high-resolution behavioral assays to capture the foraging and food intake behaviors of individual flies in real time with high temporal resolution. Using these methods, we showed that flies regulate their food ingestion and foraging behaviors by integrating metabolic state and taste/nutritional information in the brain. We further investigated the mechanisms by which a novel class of interneurons (IN1) regulates sugar ingestion. We demonstrated that IN1 neurons regulate sugar ingestion through their bi- directional communication with the fly gastrointestinal tract. Over the next five years, in this R35 MIRA grant, we aim to reveal the molecular pathways that regulate the activity of IN1 neurons in different metabolic states and determine how they become persistently active during sugar ingestion. We will also identify and characterize the functions of central and peripheral neural circuits that interact with IN1 neurons to regulate food intake, foraging, and other innate behaviors. Functional dissection of IN1 circuitry will lead us to the fundamental principles by which the nervous system regulates foraging and food intake. Additionally, we will characterize the molecular and anatomical architecture of the fly enteric nervous system and the functions of enteric neurons in regulating food ingestion and nutrient preference. Understanding the fundamental neural and molecular mechanisms underlying foraging, food intake, and nutrient sensing in flies will help us uncover conserved pathways and principles that regulate these vital behaviors across different species. Once we discover key neurogenetic mechanisms underlying food intake and foraging, we can search for similar processes in more complex mammalian models and in patients suffering from obesity or eating disorders to develop treatment strategies that intervene in the pathogenesis of these life-threatening diseases.