XXXIX Annual Meeting of the Association for Chemoreception Sciences Hyatt Regency Coconut Point, Bonita Springs, Florida

The olfactory bulb (OB) output neurons, the mitral and tufted cells project in a distributed fashion to several brain areas including the piriform cortex (PC) and anterior olfactory nucleus (AON). These, in turn, send massive glutamatergic projections back into the OB. We recently reported (Otazu, Chae, et al., Neuron, 2015) that pharmacological inactivation of the anterior piriform cortex (APC) increases odor responsiveness and pairwise similarity of mitral cells, but has little impact on tufted cells. Therefore, we proposed that PC feedback specifically acts on mitral cell representations to enable odor separation, while only mildly altering tufted cell responses. However, how feedback from AON controls these two classes of OB output neurons remains unknown to date. We used multiphoton calcium imaging (GCaMP3) to monitor the odor responses of mitral and tufted cells in awake head-fixed mice. Pharmacological inactivation of the AON increased preferentially the odor responsiveness and pairwise similarity of tufted versus mitral cells. This is complementary to the effect observed when suppressing the piriform cortex. We have further monitored the activity (GCaMP6f) of granule cells, the OB inhibitory interneurons that receive most of top-down feedback from APC and AON. Feedback from AON and APC modulated GC activity in a cell and concentration specific fashion, independent of odor identity. We propose that feedback from PC and AON differentially modulates the two OB output channels. We are currently investigating whether distinct sets of GCs are differentially controlled by feedback originating in the APC vs. AON. Furthermore, we explore optogenetic strategies, and locally suppress distinct feedback signals to the bulb, to assess their contributions to olfactory behaviors.