TY - JOUR
T1 - Sensory deprivation after focal ischemia in mice accelerates brain remapping and improves functional recovery through Arc-dependent synaptic plasticity
AU - Kraft, Andrew W.
AU - Bauer, Adam Q.
AU - Culver, Joseph P.
AU - Lee, Jin Moo
N1 - Funding Information:
This work was supported, in part, by NIH grants R01NS084028, R01NS085419 (J.-M.L.), F31NS089135 (A.W.K.), R01NS078223 (J.P.C.), P01NS080675 (J.P.C.), and K25NS083754 (A.Q.B.) and by American Heart Association grants 13POST14240023 (A.Q.B.) and 14PRE18410013 (A.W.K.). Author contributions: A.W.K., A.Q.B., J.P.C., and J.-M.L. designed all experiments. A.W.K. performed animal experiments and collected imaging data for all experiments. A.W.K. and A.Q.B. performed image processing, image analysis, and statistical analysis with oversight from J.P.C. and J.-M.L. A.W.K. and J.-M.L. wrote the manuscript with input from all coauthors. All authors read and approved the final manuscript. J.-M.L. supervised all aspects of the project. Competing interests: The authors declare that they have no competing interests.
Publisher Copyright:
Copyright © 2018 The Authors.
PY - 2018/1/31
Y1 - 2018/1/31
N2 - Recovery after stroke, a major cause of adult disability, is often unpredictable and incomplete. Behavioral recovery is associated with functional reorganization (remapping) in perilesional regions, suggesting that promoting this process might be an effective strategy to enhance recovery. However, the molecular mechanisms underlying remapping after brain injury and the consequences of its modulation are poorly understood. Focal sensory loss or deprivation has been shown to induce remapping in the corresponding brain areas through activity-regulated cytoskeleton-associated protein (Arc)-mediated synaptic plasticity. We show that targeted sensory deprivation via whisker trimming in mice after induction of ischemic stroke in the somatosensory cortex representing forepaw accelerates remapping into the whisker barrel cortex and improves sensorimotor recovery. These improvements persisted even after focal sensory deprivation ended (whiskers allowed to regrow). Mice deficient in Arc, a gene critical for activity-dependent synaptic plasticity, failed to remap or recover sensorimotor function. These results indicate that post-stroke remapping occurs through Arc-mediated synaptic plasticity and is required for behavioral recovery. Furthermore, our findings suggest that enhancing perilesional cortical plasticity via focal sensory deprivation improves recovery after ischemic stroke in mice.
AB - Recovery after stroke, a major cause of adult disability, is often unpredictable and incomplete. Behavioral recovery is associated with functional reorganization (remapping) in perilesional regions, suggesting that promoting this process might be an effective strategy to enhance recovery. However, the molecular mechanisms underlying remapping after brain injury and the consequences of its modulation are poorly understood. Focal sensory loss or deprivation has been shown to induce remapping in the corresponding brain areas through activity-regulated cytoskeleton-associated protein (Arc)-mediated synaptic plasticity. We show that targeted sensory deprivation via whisker trimming in mice after induction of ischemic stroke in the somatosensory cortex representing forepaw accelerates remapping into the whisker barrel cortex and improves sensorimotor recovery. These improvements persisted even after focal sensory deprivation ended (whiskers allowed to regrow). Mice deficient in Arc, a gene critical for activity-dependent synaptic plasticity, failed to remap or recover sensorimotor function. These results indicate that post-stroke remapping occurs through Arc-mediated synaptic plasticity and is required for behavioral recovery. Furthermore, our findings suggest that enhancing perilesional cortical plasticity via focal sensory deprivation improves recovery after ischemic stroke in mice.
UR - http://www.scopus.com/inward/record.url?scp=85041675613&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.aag1328
DO - 10.1126/scitranslmed.aag1328
M3 - Article
C2 - 29386356
AN - SCOPUS:85041675613
VL - 10
JO - Science Translational Medicine
JF - Science Translational Medicine
SN - 1946-6234
IS - 426
M1 - eaag1328
ER -