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How a Little Activity can Boost CNS Regeneration

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Review of “Neural activity promotes long-distance, target-specific regeneration of adult retinal axons” from Nature Neuroscience by Stuart P. Atkinson

 “Axons in the mammalian CNS fail to regenerate after injury”. The blunt first line of a recent Nature Neuroscience paper efficiently highlights the problems that we face following injury to the brain and spinal cord [1]. But this shouldn’t lead to a lull in research activity, and indeed, it seems like a little activity may be what is needed to boost central nervous system (CNS) regeneration!

While attempting to discover the factors which limit CNS regeneration, in the hope of creating better regenerative therapies, the laboratory of Andrew D Huberman (Stanford University School of Medicine, USA) have now found that neural activity enhances accompanying axonal regeneration strategies and can allow for adult CNS neurons to appropriately reconnect following injury [2]!

To study axonal regeneration in the CNS, the study assessed regenerative responses following crushing of retinal ganglion cell (RGC) axons, a widely used model system. In the absence of any therapeutic intervention, few axons grew past the crush site and most died. However, enhancing the electrical activity of the RGCs via high-contrast visual stimulation (or via chemogenetics) caused some of axons to regenerate past the lesion site.

But why stop there? In an attempt to further enhance this effect, the authors combined visual stimulation with another strategy known to trigger RGC axon regeneration: increased mammalian target of rapamycin (mTOR) signaling (See original study for extensive references). Excitingly, this combination had a synergistic effect and allowed some RGC axons to regenerate through lesion sites and extend down the optic nerve. Indeed, the combination was so effective that RGC axon regeneration extended and re-innervated their correct targets in the brain and mediated the partial recovery of certain visual functions and vision-driven behaviors.

This exquisitely detailed study has one main take home message: a little activity can boost CNS regeneration in adult mice! Hopefully, this fascinating study may allow us to devise new and effective treatments for those suffering from damage or disease in CNS regions.

References

  1. Liu K, Tedeschi A, Park KK, et al. Neuronal intrinsic mechanisms of axon regeneration. Annu Rev Neurosci 2011;34:131-152.
  2. Lim JH, Stafford BK, Nguyen PL, et al. Neural activity promotes long-distance, target-specific regeneration of adult retinal axons. Nat Neurosci 2016;19:1073-1084.