The contribution of lateral hypothalamus to cortical palatability coding and behavior

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Project Summary The central job of the taste system involves deciding whether a substance in the mouth should be swallowed or rejected. This job is of unique importance, in that these decisions are necessarily made after a potentially toxic stimulus is already internal. Primary gustatory cortex (GC) has proven vital for driving taste rejection behavior in situ, but it is unlikely GC is acting alone to accomplish this task. Of particular interest as a possible functional partner to GC is the lateral hypothalamus (LH), which has long been known to be centrally involved in feeding behavior, and which contains neurons producing two distinct types of palatability-related taste responses. This proposal describes work that will use multi-electrode electrophysiology, electromyography, pathway- and neuron-specific optogenetics, and complex neural and behavioral analyses to investigate whether and how GC and LH coordinate to drive consumption-related cortical firing and behavior. Dual-site electrophysiological responses from awake, tasting rats will be analyzed to determine whether and how LH and GC responses are coupled for production of palatability-related firing; further work will determine whether particular response types or neurons (i.e., orexin+ neurons, known to drive consumption) contribute to any observed LH-GC coupling. Perturbing LHGC input (and specifically the activity of orexin+ neurons) during tasting sessions will test whether and how hypothalamic input impacts GC taste response dynamics. These experiments will be the first exploration into GC-LH cooperation for taste processing and behavioral output. Over the course of this project, advanced computational training will be acquired both in the classroom and through the development of novel scripts for specific analyses. The collaborative and intimate environment within the lab and at Brandeis will nourish not only the knowledgebase (computational and beyond), but the mentorship, communication, and technical skills required to develop as an independent researcher. The combination of behavior, electrophysiology, and genetic approaches will provide invaluable insight to the taste system, ultimately improving our knowledge of the gustatory system and how taste processing and decisions are made. As we are directly investigating palatability and its relationship to behavior this clears the path for future research on disorders related to consumption and hedonics. As such, the work is related to improving human health in this era of obesity and binge-eating.