Abstract
ABSTRACTPrimary sensory axons stop regenerating as they enter the spinal cord, resulting in incurable sensory loss. What arrests them remains unknown. We previously showed that axons stop by forming synaptic contacts with unknown non-neuronal cells. Here, we identified these cells in adult mice as oligodendrocyte precursor cells (OPCs). We also found that only a few axons stop regenerating by forming dystrophic endings, exclusively at the CNS:PNS borderline where OPCs are absent. Most axons stop beyond the boundary in contacts with a dense network of OPC processes. Live imaging, immuno-EM and OPC-DRG co-culture show that axons are rapidly immobilized by forming functional synapses with OPCs. Remarkably, genetic OPC ablation enables many axons to continue regenerating deep into the spinal cord. These data indicate that axons stop regenerating prematurely by forming aberrant synapses with OPCs. Our findings identify OPCs a as a major regenerative barrier, providing new insights into how to promote spinal circuit restoration.
Publisher
Cold Spring Harbor Laboratory