Optogenetic and transcriptomic interrogation of enhanced muscle function in the paralyzed mouse whisker pad

Journal of Neurophysiology
Thomas J VajtayDavid J Margolis

Abstract

The functional state of denervated muscle is a critical factor in the ability to restore movement after injury- or disease-related paralysis. Here we used peripheral optogenetic stimulation and transcriptome profiling in the mouse whisker system to investigate the time course of changes in neuromuscular function following complete unilateral facial nerve transection. While most skeletal muscles rapidly lose functionality after lower motor neuron denervation, optogenetic muscle stimulation of the paralyzed whisker pad revealed sustained increases in the sensitivity, velocity, and amplitude of whisker movements, and reduced fatigability, starting 48 h after denervation. RNA-seq analysis showed distinct regulation of multiple gene families in denervated whisker pad muscles compared with the atrophy-prone soleus, including prominent changes in ion channels and contractile fibers. Together, our results define the unique functional and transcriptomic landscape of denervated facial muscles and have general implications for restoring movement after neuromuscular injury or disease. NEW & NOTEWORTHY Optogenetic activation of muscle can be used to noninvasively induce movements and probe muscle function. We used this technique in mice to ...Continue Reading

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Citations

Aug 12, 2020·Connective Tissue Research·Elahe GanjiMegan L Killian

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Datasets Mentioned

BETA
GSE58669
GSE121590

Methods Mentioned

BETA
RNA-seq
biopsy
PCR

Software Mentioned

MATLAB
ENSEMBL
Myog
ImageJ
bcl2fastq2 -
lme4 R package
Python
ParDRe
Fastp
Sleuth

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