Deleting Adult OPC expressed Voltage Gated Calcium Channel Subunits Enhances Mouse Skilled Forelimb Function
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Date
2025-05
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The Ohio State University
Abstract
Myelin disruption after spinal cord injuries (SCI) or demyelinating diseases causes axonal conduction failure, impairing neurological function. In the central nervous system (CNS), myelin sheaths are formed by oligodendrocytes which are differentiated from their progenitors, oligodendrocyte precursor cells (OPCs). OPCs express various voltage-gated ion channels, including voltage-gated calcium channels (VGCCs). α2δ subunits of the VGCCs play essential roles in increasing the density of calcium channels and the channel's conductance. α2δ subunits, particularly α2δ1 subunits, are highly expressed in OPCs. This study investigates whether OPC-expressed α2δ1 plays a functional role in mediating mouse behavioral performance. Using a tamoxifen-inducible conditional knockout mouse model, we specifically deleted Cacna2d1, the gene encoding α2δ1subunits, in OPCs from adulthood. The assessment of behavioral performance on the horizontal ladder rung walking test began prior to and continued for 5 weeks after tamoxifen administration. Our analysis shows that deleting adult OPC-expressed Cacna2d1 significantly improved the correct forelimb placement. As the horizontal ladder rung walking test requires sensory-motor integration for precise forelimb placement, our findings suggest that OPC-expressed α2δ1 not only regulates oligodendrocyte density in adulthood but also promotes complex neurological function, likely through facilitating myelin adaptation.
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Neuroscience, Oligodendrocyte Precursor Cells (OPCs), Voltage Gated Calcium Channels (VGCC), Alpha2delta1 (A2d1), Horizontal Ladder Rung Test, Spinal Cord