GSBS Dissertations and Theses

ORCID ID

0000-0001-5377-0648

Publication Date

2019-04-02

Document Type

Doctoral Dissertation

Academic Program

Neuroscience

Department

Neurobiology

First Thesis Advisor

Yang Xiang

Keywords

Neuroscience, Neurobiology, Drosophila, Neural Regeneration, Neural Bursting, Neural Activity

Abstract

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/wdb9-8243

Rights and Permissions

Licensed under a Creative Commons license

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Available for download on Sunday, May 31, 2020

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