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The coding of cutaneous temperature in the spinal cord

Nature Neuroscience volume 19, pages 12011209 (2016) | Download Citation

Abstract

The spinal cord is the initial stage that integrates temperature information from peripheral inputs. Here we used molecular genetics and in vivo calcium imaging to investigate the coding of cutaneous temperature in the spinal cord in mice. We found that heating or cooling the skin evoked robust calcium responses in spinal neurons, and their activation threshold temperatures distributed smoothly over the entire range of stimulation temperatures. Once activated, heat-responding neurons encoded the absolute skin temperature without adaptation and received major inputs from transient receptor potential (TRP) channel V1 (TRPV1)-positive dorsal root ganglion (DRG) neurons. By contrast, cold-responding neurons rapidly adapted to ambient temperature and selectively encoded temperature changes. These neurons received TRP channel M8 (TRPM8)-positive DRG inputs as well as novel TRPV1+ DRG inputs that were selectively activated by intense cooling. Our results provide a comprehensive examination of the temperature representation in the spinal cord and reveal fundamental differences in the coding of heat and cold.

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Acknowledgements

We thank L. Luo for his generous support during the entire project, Z. Shen for initial experiments and G. Kamalani for assistance; and B. Barres (Stanford University) and D. Julius (University of California, San Francisco) for Mgfap-cre and Trpa1 knockout mice. We are grateful to X. Gao, C. Guenthner, B. Weissbourd and members of the Chen laboratory for comments on the manuscript. This work was supported by grants from the intramural research program of NIDCR (M.A.H.), and the Whitehall Foundation, Terman Fellowship and start-up funding from Stanford University (X.C.).

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Affiliations

  1. Department of Biology, Stanford University, Stanford, California, USA.

    • Chen Ran
    •  & Xiaoke Chen
  2. National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.

    • Mark A Hoon

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Contributions

C.R. and X.C. designed the study. C.R. conducted imaging experiments. C.R. and X.C. analyzed data. M.A.H. provided TRPM8- and TRPV1-DTR mice, and performed in situ hybridization experiments. C.R. and X.C. wrote the paper with help from M.A.H. X.C. supervised the research.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Xiaoke Chen.

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DOI

https://doi.org/10.1038/nn.4350

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