Electrical activity suppresses axon growth through Cav1.2 channels in adult primary sensory neurons

Joana Enes, Nicole Langwieser, Jörg Ruschel, Melissa M. Carballosa-Gonzalez, Achim Klug, Matthias H. Traut, Bhavna Ylera, Sabina Tahirovic, Franz Hofmann, Valentin Stein, Sven Moosmang, Ian D. Hentall, Frank Bradke

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54 Scopus citations

Abstract

Background: Primary sensory neurons of the dorsal root ganglia (DRG) regenerate their spinal cord axon if the peripheral nerve axon has previously been cut. This conditioning lesion confers axon growth competence to the neurons. However, the signal that is sensed by the cell upon peripheral lesion to initiate the regenerative response remains elusive. Results: We show here that loss of electrical activity following peripheral deafferentiation is an important signal to trigger axon regrowth. We first verified that firing in sensory fibers, as recorded from dorsal roots in vivo, declined after peripheral lesioning but was not altered after central lesioning. We found that electrical activity strongly inhibited axon outgrowth in cultured adult sensory neurons. The inhibitory effect depended on the L-type voltage-gated Ca2+ channel current and involved transcriptional changes. After a peripheral lesion, the L-type current was consistently diminished and the L-type pore-forming subunit, Cav1.2, was downregulated. Genetic ablation of Ca v1.2 in the nervous system caused an increase in axon outgrowth from dissociated DRG neurons and enhanced peripheral nerve regeneration in vivo. Conclusions: Our data indicate that cessation of electrical activity after peripheral lesion contributes to the regenerative response observed upon conditioning and might be necessary to promote regeneration after central nervous system injury.

Original languageEnglish (US)
Pages (from-to)1154-1164
Number of pages11
JournalCurrent Biology
Volume20
Issue number13
DOIs
StatePublished - Jul 13 2010

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Keywords

  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Enes, J., Langwieser, N., Ruschel, J., Carballosa-Gonzalez, M. M., Klug, A., Traut, M. H., Ylera, B., Tahirovic, S., Hofmann, F., Stein, V., Moosmang, S., Hentall, I. D., & Bradke, F. (2010). Electrical activity suppresses axon growth through Cav1.2 channels in adult primary sensory neurons. Current Biology, 20(13), 1154-1164. https://doi.org/10.1016/j.cub.2010.05.055