Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex

Nat Neurosci. 2018 Jan;21(1):120-129. doi: 10.1038/s41593-017-0029-5. Epub 2017 Dec 11.

Abstract

Activity-dependent transcriptional responses shape cortical function. However, a comprehensive understanding of the diversity of these responses across the full range of cortical cell types, and how these changes contribute to neuronal plasticity and disease, is lacking. To investigate the breadth of transcriptional changes that occur across cell types in the mouse visual cortex after exposure to light, we applied high-throughput single-cell RNA sequencing. We identified significant and divergent transcriptional responses to stimulation in each of the 30 cell types characterized, thus revealing 611 stimulus-responsive genes. Excitatory pyramidal neurons exhibited inter- and intralaminar heterogeneity in the induction of stimulus-responsive genes. Non-neuronal cells showed clear transcriptional responses that may regulate experience-dependent changes in neurovascular coupling and myelination. Together, these results reveal the dynamic landscape of the stimulus-dependent transcriptional changes occurring across cell types in the visual cortex; these changes are probably critical for cortical function and may be sites of deregulation in developmental brain disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Gene Expression Regulation / physiology
  • Gene Ontology
  • Light
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Inhibition / physiology
  • Neuroglia / physiology*
  • Neurons / cytology
  • Neurons / physiology*
  • Neurovascular Coupling / physiology
  • Photic Stimulation
  • Proto-Oncogene Proteins c-fos / metabolism
  • Signal Transduction / physiology
  • Single-Cell Analysis / methods
  • Statistics, Nonparametric
  • Transcription, Genetic / physiology*
  • Transcriptome / physiology*
  • Visual Cortex / cytology*
  • Visual Pathways

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Nerve Tissue Proteins
  • Npas4 protein, mouse
  • Proto-Oncogene Proteins c-fos