Abstract
Sensory systems must perform the dual and opposing tasks of being sensitive to weak stimuli while also maintaining information content in dense and variable sensory landscapes. This occurs in the olfactory system, where OSNs are highly sensitive to low concentrations of odors and maintain discriminability in complex odor environments. How olfactory sensory neurons (OSNs) maintain both sensitivity and sparsity is poorly understood. Here, we investigated whether the calcium-activated chloride channel, TMEM16B, may support these dual roles in OSNs in both male and female mice. We used multiphoton microscopy to image the stimulus-response density of OSNs in the olfactory epithelium. In TMEM16B knockout mice, we found that sensory representations were denser, and the magnitude of OSN responses was increased. Behaviorally, these changes in sensory representations were associated with an increased aversion to the odorant trimethylamine, which switches perceptual valence as its concentration increases, and a decreased efficiency of olfactory-guided navigation. Our results indicate that the calcium-activated chloride channel TMEM16B sparsens sensory representations in the peripheral olfactory system and contributes to efficient integrative olfactory-guided behaviors.Significance Statement Sensory systems must build internal neural representations of stimuli found in the external environment. In the olfactory system, molecules that give rise to the perception of odors are detected by olfactory sensory neurons within the nose. Upon odorant binding to sensory neurons, a biochemical signaling cascade transduces neural signals that other areas of the brain can then read out. A key component of this cascade is the calcium-activated chloride channel TMEM16B. We found that despite its role in amplifying transduction currents in olfactory sensory neurons, TMEM16B paradoxically constrains their output, thereby limiting information transfer to the brain. Our findings also indicate that TMEM16B plays an important role in how animals detect and perceive odors.