Differences in olfactory bulb mitral cell spiking with ortho- and retronasal stimulation revealed by data-driven models

The majority of olfaction studies focus on orthonasal stimulation where odors enter via the front nasal cavity, while retronasal olfaction, where odors enter the rear of the nasal cavity during feeding, is understudied. The coding of retronasal odors via coordinated spiking of neurons in the olfactory bulb (OB) is largely unknown despite evidence that higher level processing is different than orthonasal. To this end, we use multi-electrode array in vivo recordings of rat OB mitral cells (MC) in response to a food odor with both modes of stimulation, and find significant differences in evoked firing rates and spike count covariances (i.e., noise correlations). Differences in spiking activity often have implications for sensory coding, thus we develop a single-compartment biophysical OB model that is able to reproduce key properties of important OB cell types. Prior experiments in olfactory receptor neurons (ORN) showed retro stimulation yields slower and spatially smaller ORN inputs than with ortho, yet whether this is consequential for OB activity remains unknown. Indeed with these specifications for ORN inputs, our OB model captures the salient trends in our OB data. We also analyze how first and second order ORN input statistics dynamically transfer to MC spiking statistics with a phenomenological linear-nonlinear filter model, and find that retro inputs result in larger linear filters than ortho inputs. Finally, our models show that the temporal profile of ORN is crucial for capturing our data and is thus a distinguishing feature between ortho and retro stimulation, even at the OB. Using data-driven modeling, we detail how ORN inputs result in differences in OB dynamics and MC spiking statistics. These differences may ultimately shape how ortho and retro odors are coded.Author summary: Olfaction is a key sense for many cognitive and behavioral tasks, and is particularly unique because odors can naturally enter the nasal cavity from the front or rear, i.e., ortho- and retro-nasal, respectively. Yet little is known about the differences in coordinated spiking in the olfactory bulb with ortho versus retro stimulation, let alone how these different modes of olfaction may alter coding of odors. We simultaneously record many cells in rat olfactory bulb to assess the differences in spiking statistics, and develop a biophysical olfactory bulb network model to study the reasons for these differences. Using theoretical and computational methods, we find that the olfactory bulb transfers input statistics differently for retro stimulation relative to ortho stimulation. Furthermore, our models show that the temporal profile of inputs is crucial for capturing our data and is thus a distinguishing feature between ortho and retro stimulation, even at the olfactory bulb. Understanding the spiking dynamics of the olfactory bulb with both ortho and retro stimulation is a key step for ultimately understanding how the brain codes odors with different modes of olfaction.