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

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

Author information

1
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
2
Society of Fellows, Harvard University, Cambridge, MA, USA.
3
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA.
4
Image and Data Analysis Core, Harvard Medical School, Boston, MA, USA.
5
Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
6
Vilnius University Institute of Biotechnology, Vilnius, Lithuania.
7
ICCB-L Single Cell Core, Harvard Medical School, Boston, MA, USA.
8
Program for Bioinformatics and Integrative Genomics, Graduate School of Arts and Science, Division of Medical Sciences, Harvard University, Cambridge, MA, USA.
9
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA. bernardo_sabatini@hms.harvard.edu.
10
Department of Neurobiology, Harvard Medical School, Boston, MA, USA. michael_greenberg@hms.harvard.edu.

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.

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