Modulation of food preference through the integration of gustatory and olfactory circuits

About This Grant

Neural circuits allow animals to gather various types of sensory information from the complex environment and integrate this information to produce the appropriate behavioral responses. To decide whether to ingest potential food substances, animals must discriminate between nutrients and toxins. To this end, they integrate sensory information, such as taste, smell, texture, temperature, and visual cues, with internal states, such as hunger and satiety. It is well established that the integration of taste and smell, perceived as flavor in humans, is especially important for food discrimination. However, the precise points of integration between the taste and smell circuits remain unknown in humans due to the complexity of the nervous system. Studies monitoring feeding behavior upon smell stimulation in the fruit fly, Drosophila melanogaster, suggest that the taste and smell circuits also integrate in the fly. Since the neural circuits in fruit flies are simpler than those in humans, flies are an ideal organism for evaluating the anatomical and functional connections between taste and smell. Our laboratory has developed trans-Tango, a method for neural circuit mapping and manipulation in fruit flies. Using trans-Tango, we mapped the first and second-order neurons in the taste and smell circuits, showing that gustatory receptor neurons, which detect tastants, and olfactory receptor neurons, which detect odors, relay information to gustatory and olfactory projection neurons, respectively. Some of these projection neurons target the same higher-order brain areas, suggesting the possibility that shared neurons exist that integrate sensory inputs from both systems to influence feeding behavior. This proposal takes a two-pronged approach to investigate the integration of the gustatory and olfactory circuits. First, I will test how olfactory inputs affect feeding by activating, or silencing, olfactory projection neurons tuned to food-derived odors. In these studies, I will use the OptoPAD paradigm to measure feeding. I hypothesize that activating neurons tuned to attractive odors would enhance feeding, while activating those tuned to aversive odors would suppress it. Second, I will identify neurons in the lateral horn that receive inputs from both gustatory and olfactory projection neurons and integrate these inputs to produce the appropriate feeding responses. To this end, I have been developing trans-Tango(hub), a tool for identifying circuit nodes of integration. My experiments will determine whether these nodes maintain the valence of the stimuli. Further, since the gustatory and olfactory systems in insects and mammals are functionally homologous, identifying the mechanisms of this multisensory integration in fruit flies will provide insight into how the perception of flavor is formed in humans. This is crucial for understanding the pathologies associated with olfactory deficiencies, such as anosmia and hyposmia, and gustatory deficiencies, such as ageusia. Finally, this research program is at the core of a training plan that includes activities to develop professional skills for preparing Angel Okoro for a career in academic research.