Optogenetic Food Odor Avoidance Assay

Appetite is tightly linked to the sensory experience of feeding, including the smell, taste, and sight of food. Sensory perception can affect the palatability of food, modulating appetite beyond homeostatic requirements. Hypothalamic neurons that govern feeding are responsive to sensory cues associated with food, including food odors. However, the circuit mechanisms by which sensory information is processed and relayed to feeding nodes to affect feeding behavior is not well understood. Recent work has identified a population of excitatory basal forebrain neurons that modulate potent appetite suppression, as well as respond to food-associated and innately aversive odorants. To investigate this circuitry, we stereotaxically targeted virus expressing Cre-dependent channelrhodopsin to the basal forebrain and implanted fiber optic cannulas over the injection site. Mice were allowed to recover and underwent training to form a passive association of chow with a unique monomolecular odorant. After training, mice were fasted overnight, and were then presented with both the food-associated odor as well as a similar, novel odor in zones of an arena with and without photostimulation. To evaluate whether stimulation of this circuitry influenced sensory modulation of feeding behavior, video recording and behavioral tracking analysis were used to compare time spent investigating either odor. Thus, this protocol provides a useful paradigm to assay the contribution of different circuits in appetitive and aversive behaviors.