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Abstract

Throughout life, oligodendrocyte progenitor cells (OPCs) proliferate and differentiate into myelinating oligodendrocytes. OPCs express cell surface receptors and channels that allow them to detect and respond to neuronal activity, including voltage-gated calcium channel (VGCC)s. The major L-type VGCC expressed by developmental OPCs, CaV1.2, regulates their differentiation. However, it is unclear whether CaV1.2 similarly influences OPC behavior in the healthy adult central nervous system (CNS). To examine the role of CaV1.2 in adulthood, we conditionally deleted this channel from OPCs by administering tamoxifen to P60 Cacna1c fl/fl (control) and Pdgfrα-CreER:: Cacna1c fl/fl (CaV1.2-deleted) mice. Whole cell patch clamp analysis revealed that CaV1.2 deletion reduced L-type voltage-gated calcium entry into adult OPCs by ~60%, confirming that it remains the major L-type VGCC expressed by OPCs in adulthood. The conditional deletion of CaV1.2 from adult OPCs significantly increased their proliferation but did not affect the number of new oligodendrocytes produced or influence the length or number of internodes they elaborated. Unexpectedly, CaV1.2 deletion resulted in the dramatic loss of OPCs from the corpus callosum, such that 7 days after tamoxifen administration CaV1.2-deleted mice had an OPC density ~42% that of control mice. OPC density recovered within 2 weeks of CaV1.2 deletion, as the lost OPCs were replaced by surviving CaV1.2-deleted OPCs. As OPC density was not affected in the motor cortex or spinal cord, we conclude that calcium entry through CaV1.2 is a critical survival signal for a subpopulation of callosal OPCs but not for all OPCs in the mature CNS.

Item Type:	Article
Authors/Creators:	Pitman, KA and Ricci, R and Gasperini, R and Beasley, S and Pavez, M and Charlesworth, J and Foa, L and Young, KM
Keywords:	myelin, voltage-gated, activity, cell death, CaV1.2, Cacna1C, NG2, apoptosis, calcium, corpus callosum, motor cortex, oligodendrocyte, proliferation, survival, voltage-gated calcium channel
Journal or Publication Title:	Glia
Publisher:	Wiley-Liss
ISSN:	0894-1491
DOI / ID Number:	10.1002/glia.23723
Copyright Information:	© 2019 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/
Related URLs:	Google Scholar: Pitman, KA Google Scholar: Charlesworth, J UTAS Profile: Charlesworth, J Google Scholar: Foa, L UTAS Profile: Foa, L UTAS Profile: Young, KM
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