4.8 Article

A transcriptional rheostat couples past activity to future sensory responses

Journal

CELL
Volume 184, Issue 26, Pages 6326-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2021.11.022

Keywords

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Funding

  1. NIH [R011DC016222, U19 NS112953, F31DC019017]
  2. Simons Collaboration on the Global Brain
  3. Brain Research Foundation
  4. Tan Yang Center at Harvard Medical School
  5. Japan Society for the Promotion of Science
  6. Louis Perry Jones Fund
  7. Tan Yang Center
  8. NSF Graduate Research Fellowship

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The research found that each subtype of olfactory sensory neuron in mice has a unique transcriptome, which is precisely determined by interactions between its odorant receptor and the environment. This transcriptional variation is systematically organized to support sensory adaptation and accurately predict responses to odors. The findings suggest a general model where structured transcriptional variation within a cell type reflects individual experience.
Animals traversing different environments encounter both stable background stimuli and novel cues, which are thought to be detected by primary sensory neurons and then distinguished by downstream brain circuits. Here, we show that each of the 1,000 olfactory sensory neuron (OSN) subtypes in the mouse harbors a distinct transcriptome whose content is precisely determined by interactions between its odorant receptor and the environment. This transcriptional variation is systematically organized to support sensory adaptation: expression levels of more than 70 genes relevant to transforming odors into spikes continuously vary across OSN subtypes, dynamically adjust to new environments over hours, and accurately predict acute OSN-specific odor responses. The sensory periphery therefore separates salient signals from predictable background via a transcriptional rheostat whose moment-to-moment state reflects the past and constrains the future; these findings suggest a general model in which structured transcriptional variation within a cell type reflects individual experience.

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