Motivational systems are tightly tuned in nature, however laboratory settings tend to focus attention toward one aspect of behavior for simplicity purposes. Appetite regulation is an extremely vital motivational system and dissecting out the neural circuits regulating this complex process is imperative in our fight against obesity and feeding-associated diseases. Here, we are proposing to study how hunger and satiety signals are associated with other motivational processes such as fear and anxiety. Caged rodents are normally presented with food ad libitum, however to test hunger circuits, mice can be fasted or alternatively hunger-promoting neurons can be artificially manipulated. Mice will undergo various paradigms to strengthen hunger signals and presented with visual, auditory and/or olfactory cues that innately drive anxiety, such as the presence of predatory urine or an intruder animal. Studies such as these will allow us to unravel circuit mechanisms integrating motivational systems such as hunger versus fear. We will use a library of Cre-expressing mice (AGRP, POMC, MC4R) as well as Cre-dependent AAV-vectors (ChR2, hM3dq, synaptophysin) in a number of behavioral paradigms including place preference and sociability tests.

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Liang, Jing; Krashes, Michael J (2017) AgRP Accountants Compute Caloric Cost. Cell Rep 21:2647-2648
Duerrschmid, Clemens; He, Yanlin; Wang, Chunmei et al. (2017) Asprosin is a centrally acting orexigenic hormone. Nat Med 23:1444-1453
Ghitani, Nima; Barik, Arnab; Szczot, Marcin et al. (2017) Specialized Mechanosensory Nociceptors Mediating Rapid Responses to Hair Pull. Neuron 95:944-954.e4
Burnett, C Joseph; Krashes, Michael J (2016) Acute Glucose Response Properties Beyond Feeding. Trends Mol Med 22:356-358
Krashes, Michael J; Lowell, Bradford B; Garfield, Alastair S (2016) Melanocortin-4 receptor-regulated energy homeostasis. Nat Neurosci 19:206-19
Garfield, Alastair S; Li, Chia; Madara, Joseph C et al. (2015) A neural basis for melanocortin-4 receptor-regulated appetite. Nat Neurosci 18:863-71
Vardy, Eyal; Robinson, J Elliott; Li, Chia et al. (2015) A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior. Neuron 86:936-946