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Patterned Neuronal Activities Dictate Cell Type-specific Axon Regeneration

Kendra Takle Ruppell, Fei Wang, Feng Li, Ye Shang, Jiaxin Gong, Pavi Guttipatti, Yuanquan Song, Yang Xiang
doi: https://doi.org/10.1101/799635
Kendra Takle Ruppell
1Department of Neurobiology, Program of Neuroscience, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
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Fei Wang
1Department of Neurobiology, Program of Neuroscience, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
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Feng Li
2Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
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Ye Shang
1Department of Neurobiology, Program of Neuroscience, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
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Jiaxin Gong
5Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
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Pavi Guttipatti
2Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
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Yuanquan Song
2Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
3Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Yang Xiang
1Department of Neurobiology, Program of Neuroscience, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
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  • For correspondence: yang.xiang@umassmed.edu
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Abstract

Injured neurons exhibit cell type-specific axon regeneration, but the underlying mechanisms remain elusive. Two subtypes of Drosophila sensory neurons show distinct regenerative competence. Here, we show that axotomy induces long-lasting burst firing and Ca2+ spikes specifically in the regenerative subtype. Genetic silencing of firing in the regenerative subtype inhibits regeneration. Optogenetic stimulation of the non-regenerative subtype reveals that activity patterns critically determine regeneration; burst firing triggers Ca2+ spikes and suffices to induce regeneration, while tonic firing fails to induce Ca2+ spikes and regeneration. We further show the L-type Ca2+ channel, Dmca1D, regulates Ca2+ spikes and regeneration. Intriguingly, the regenerative neuronal subtype expresses higher levels of Dmca1D, and overexpression of Dmca1D in the non-regenerative subtype facilitates regeneration. Our studies indicate that injury induces cell type-specific neuronal activities, which act through Ca2+ spikes to govern regeneration, and suggest that precise control of neuronal activity patterns is an effective way to promote regeneration.

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Posted October 10, 2019.
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Patterned Neuronal Activities Dictate Cell Type-specific Axon Regeneration
Kendra Takle Ruppell, Fei Wang, Feng Li, Ye Shang, Jiaxin Gong, Pavi Guttipatti, Yuanquan Song, Yang Xiang
bioRxiv 799635; doi: https://doi.org/10.1101/799635
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Patterned Neuronal Activities Dictate Cell Type-specific Axon Regeneration
Kendra Takle Ruppell, Fei Wang, Feng Li, Ye Shang, Jiaxin Gong, Pavi Guttipatti, Yuanquan Song, Yang Xiang
bioRxiv 799635; doi: https://doi.org/10.1101/799635

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