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Transcriptional adaptation couples past experience and future sensory responses
Sensory adaptation allows neurons to minimize responses to persistent or repetitive stimuli, thereby emphasizing novel cues. Traditionally, it is thought that the periphery is a stable messenger of the outside world, while the brain flexibly adapts to changes in the environment. In the olfactory system, olfactory sensory neurons (OSNs) in the nose detect odors through odorant receptors and each OSN expresses only one receptor out of >1000 in mice and ~300 in humans. These OSNs have been thought to reliably respond to the same stimuli in the same way irrespective of their experience. By using single cell RNA-sequencing and in vivo calcium imaging, we recently revealed that OSNs adapt to the environment by reconfiguring their transcriptomes over timescales of hours to days. We find that each of the ~1000 receptor-defined mouse OSN subtypes harbors a distinct transcriptome. The content of each subtype-specific transcriptome includes >70 functional genes relevant to converting odor-receptor binding to action potentials, e.g., GPCR signaling factors and ion channels, and is precisely determined by interactions between the expressed odorant receptors and the environment. Critically, we find the patterns of functional gene expression predictably influences future odor responses. This discovery identified a novel form of adaptation and revealed unexpected flexibility in peripheral sensory codes. It also suggests a general model in which transcriptional variation within a single cell type reflects activity history of individual cells and contributes to optimize their functions. I will also briefly discuss about our ongoing work to comprehensively characterize odor representations at the periphery and examine how they are transformed in the brain.
Host: Dr. Alberto Stolfi