Long-range functional loops in the mouse olfactory system and their roles in computing odor identity.

Elucidating the neural circuits supporting odor identification remains an open challenge. Here, we analyze the contribution of the two output cell types of the mouse olfactory bulb (mitral and tufted cells) to decode odor identity and concentration and its dependence on top-down feedback from their respective major cortical targets: piriform cortex versus anterior olfactory nucleus. We find that tufted cells substantially outperform mitral cells in decoding both odor identity and intensity. Cortical feedback selectively regulates the activity of its dominant bulb projection cell type and implements different computations. Piriform feedback specifically restructures mitral responses, whereas feedback from the anterior olfactory nucleus preferentially controls the gain of tufted representations without altering their odor tuning. Our results identify distinct functional loops involving the mitral and tufted cells and their cortical targets. We suggest that in addition to the canonical mitral-to-piriform pathway, tufted cells and their target regions are ideally positioned to compute odor identity.

Mosaic representations of odors in the input and output layers of the mouse olfactory bulb.

The elementary stimulus features encoded by the olfactory system remain poorly understood. We examined the relationship between 1,666 physical-chemical descriptors of odors and the activity of olfactory bulb inputs and outputs in awake mice. Glomerular and mitral and tufted cell responses were sparse and locally heterogeneous, with only a weak dependence of their positions on physical-chemical properties. Odor features represented by ensembles of mitral and tufted cells were overlapping but distinct from those represented in glomeruli, which is consistent with an extensive interplay between feedforward and feedback inputs to the bulb. This reformatting was well described as a rotation in odor space. The physical-chemical descriptors accounted for a small fraction in response variance, and the similarity of odors in the physical-chemical space was a poor predictor of similarity in neuronal representations. Our results suggest that commonly used physical-chemical properties are not systematically represented in bulbar activity and encourage further searches for better descriptors of odor space.

Cortical Feedback Decorrelates Olfactory Bulb Output in Awake Mice.

The olfactory bulb receives rich glutamatergic projections from the piriform cortex. However, the dynamics and importance of these feedback signals remain unknown. Here, we use multiphoton calcium imaging to monitor cortical feedback in the olfactory bulb of awake mice and further probe its impact on the bulb output. Responses of feedback boutons were sparse, odor specific, and often outlasted stimuli by several seconds. Odor presentation either enhanced or suppressed the activity of boutons. However, any given bouton responded with stereotypic polarity across multiple odors, preferring either enhancement or suppression. Feedback representations were locally diverse and differed in dynamics across bulb layers. Inactivation of piriform cortex increased odor responsiveness and pairwise similarity of mitral cells but had little impact on tufted cells. We propose that cortical feedback differentially impacts these two output channels of the bulb by specifically decorrelating mitral cell responses to enable odor separation.