Serial transformations in the olfactory system - Abstract The olfactory system transforms odor chemistry into perception. The neural centers that implement this transformation — in the nose, the olfactory bulb and in the cortex — serially reshape odor representations to support odor discrimination, odor categorization and perceptual stability. While, as a field, we have accumulated significant data about the tuning properties of the olfactory bulb and the olfactory cortex (typically in isolation and with arbitrarily selected stimuli), we lack an understanding of how odor chemical information — especially about odor relationships — is systematically transformed as it passes from receptors to cortex to enable perception. Characterizing this serial transformation of odor space is essential if we are to understand how discrimination and generalization are balanced to enable perception and to facilitate learning. In addition, recent results have significantly muddied our understanding of how the olfactory system maintains perceptual constancy. Odors are detected by olfactory sensory neurons (OSNs), each of which expresses a single odor receptor tuned to interact with a specific subset of odor chemical features. It has been traditionally though that OSN activity is determined by the strength of odor binding to its cognate receptor, and that OSNs therefore act as “labeled lines” that faithfully report the identity of whatever odor an animal is smelling. From this perspective, OSNs solve the problem of perceptual constancy by providing the brain with a reliable and stable representation of the odor world. However, we have recently showed that prior passive odor exposure (as occurs when mice are exposed to ambient home cage odors) dramatically modulates OSN gene expression, which profoundly reshapes future OSN responses to odors. As a consequence, OSN representations of odor identity and relationships are not stable as was previously thought, but instead are determined by recent odor experience. It remains unclear if and how downstream neural circuits in the olfactory bulb and cortex correct for this sort of experience-dependent variation in OSN activity, or alternatively, whether the olfactory system preserves this variation to better understand the broader context in which an odor was sensed. Here we propose Aims to unveil the serial transformations carried out by the olfactory system to facilitate both odor discrimination and generalization, and to reveal the strategies used by the olfactory bulb and cortex to contend with incoming sensory codes that are flexible rather than fixed. These experiments will systematically characterize neural odor representations across the three primary stages of mammalian odor processing, and address how experience-dependent transcriptional variation in nose OSNs influences olfactory codes and function in the higher brain.
