Hunger-dependent Control of Olfactory Cortical Circuits Regulates Food-seeking Behavior

We are all familiar with the scenario, “Oh, what’s that (good) smell?” Food searching and energy intake is essential to survival of all animals. The availability of metabolic energy critically determines the state in which an animal’s behavior exists. For example, an animal will prioritize for food foraging instead of mating when energy availability is low. The olfactory sense is critical to food searching. Although much is known about the neuromodulatory processes that regulate olfaction system, little is known about how the animal’s metabolic and behavioral state regulates olfactory circuits and food searching behavior. The anterior piriform cortex (APC) is one of the largest regions of olfactory cortex and is instrumental to the formation of an odor percept. As close as just one synapse downstream of the olfactory bulb (OB), principal neurons in APC can encode for multiple features of odorants such as identity, concentration and value. However, how principal neurons and its gating by inhibitory interneurons contribute to hunger-regulated odor perception remains elusive. Our group has recently identified two distinct neuronal circuits for routing information from APC back to OB: the superficial pyramidal (SP) cell receives recurrent excitation and projects back to the OB, while the semilunar (SL) cell lacks both connections. We obtained preliminary data suggesting that inhibitory transmission in SP, but not SL, cell activity is robustly reduced by fasting. Here we propose that GABAergic circuits in APC switches the effects of fasting on enhanced food-seeking behavior. This proposal is undertaken to examine the hypothesis that hunger-dependent plasticity of inhibitory circuits control SP cell function, thereby regulating food-seeking behavior. I will use a combination of slice electrophysiology, optogenetics, food deprivation, odor search behavioral analysis, mouse genetics, and immunofluorescent staining to probe the contribution of inhibitory transmission on SP cell activity and olfaction. Objective 1 will determine how fasting alters food-searching behavior in mice and how this depends on APC circuits. Objective 2 will examine how fasting regulates excitation-inhibition (E-I) balance in the APC. Objective 3 will examine how fasting anatomically regulates specific inhibitory neurons and their synapses. Elucidating how inhibition controls principal neurons in regulating food-search behavior will provide a framework for understanding how olfaction contributes to energy homeostasis.