NEURONAL CIRCUIT MECHANISMS UNDERLYING FOOD INTAKE IN DROSOPHILA MELANOGASTER
Proper regulation of food intake is essential for the survival of all animals, including humans. Although neural circuits that regulate food intake have been extensively investigated in rodent models, the entire sensorimotor circuits that regulate food intake have not been fully elucidated in any model organism. Previously, our lab has identified Ingestion Neuron 1 (IN1) as a regulator of food intake in adult Drosophila melanogaster (Yapici et al., 2016). Here, using optogenetics and two-photon calcium imaging, I revealed that IN1 neurons receive specific excitatory input from sugar-sensing enteric Gr43a neurons. We developed a new in vivo imaging method to record the activity of enteric neurons in behaving flies. Using this new method, we captured the acute response of Gr43a enteric neurons to sucrose ingestion and demonstrated that these neurons can activate IN1. In addition, I used the connectome of an entire adult fly brain to identify the major output neurons of IN1, crop innervating enteric motor (CEM) neurons. I showed that activation of CEM neurons can block the ingested food from entering the crop (a stomach-like organ). Furthermore, activation of IN1 neurons inhibits CEM neurons, allowing ingested food to be transported to the crop for storage, facilitating the later, slower process of regurgitation and digestion. Overall, my thesis research uncovered an IN1-centered sensory-motor neural circuit that acutely responds to the nutrient composition of ingested food, thereby directly influencing food ingestion in flies. By identifying this circuit's role in integrating sensory information from ingested nutrients, we have gained insights into the real-time mechanisms by which the fly brain assesses and adjusts food intake based on nutritional quality. I anticipate that our research will yield a more comprehensive understanding of how food intake is precisely regulated through complex interactions between the central brain and the enteric nervous system. This work not only sheds light on the fundamental neurobiology of feeding but also provides a foundation for exploring similar sensory-motor pathways in other organisms, potentially offering broader insights into appetite control and nutrient-based decision-making.