Neural Bursting Activity Mediates Subtype-Specific Neural Regeneration by an L-type Calcium Channel
Authors
Ruppell, Kendra TakleFaculty Advisor
Yang XiangAcademic Program
NeuroscienceDocument Type
Doctoral DissertationPublication Date
2019-04-02Keywords
NeuroscienceNeurobiology
Drosophila
Neural Regeneration
Neural Bursting
Neural Activity
Molecular and Cellular Neuroscience
Neuroscience and Neurobiology
Metadata
Show full item recordAbstract
Axons are injured after stroke, spinal cord injury, or neurodegenerative disease such as ALS. Most axons do not regenerate. A recent report suggests that not all neurons are poor regenerators, but rather a small subset can regenerate robustly. What intrinsic property of these regenerating neurons allows them to regenerate, but not their neighbors, remains a mystery. This subtype-specific regeneration has also been observed in Drosophila larvae sensory neurons. We exploited this powerful genetic system to unravel the intrinsic mechanism of subtype-specific neuron regeneration. We found that neuron bursting activity after axotomy correlates with regeneration ability. Furthermore, neuron bursting activity is necessary for regeneration of a regenerative neuron subtype, and sufficient for regeneration of a non-regenerative neuron subtype. This optogenetically-induced regeneration is dependent on a bursting pattern, not simply overall activity increase. We conclude that neuron bursting activity is an intrinsic mechanism of subtype-specific regeneration. We then discovered through a reverse genetic screen that an L-type voltage gated calcium channel (VGCC) promotes neuron bursting and subsequent regeneration. This VGCC has high expression in the regenerative neuron and weak expression in the non-regenerative neuron. This suggests that VGCC expression level is the molecular mechanism of subtype-specific neuron regeneration. Together, our findings identify a cellular and molecular intrinsic mechanism of subtype-specific regeneration, which is why some neurons are able to regenerate while the majority of neurons do not. Perhaps VGCC activation or neuron activity pattern modulation could be used therapeutically for patients with nerve injury.DOI
10.13028/wdb9-8243Permanent Link to this Item
http://hdl.handle.net/20.500.14038/31252Rights
Licensed under a Creative Commons licenseDistribution License
http://creativecommons.org/licenses/by-nc/4.0/ae974a485f413a2113503eed53cd6c53
10.13028/wdb9-8243
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Except where otherwise noted, this item's license is described as Licensed under a Creative Commons license
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