Homotopic contralesional excitation suppresses spontaneous circuit repair and global network reconnections following ischemic stroke
(2022) In eLife 11.- Abstract
Understanding circuit-level manipulations that affect the brain’s capacity for plasticity will inform the design of targeted interventions that enhance recovery after stroke. Following stroke, increased contralesional activity (e.g. use of the unaffected limb) can negatively influence recovery, but it is unknown which specific neural connections exert this influence, and to what extent increased contralesional activity affects systems-and molecular-level biomarkers of recovery. Here, we combine optogenetic photostimulation with optical intrinsic signal imaging (OISI) to examine how contralesional excitatory activity affects cortical remodeling after stroke in mice. Following photothrombosis of left primary somatosensory forepaw (S1FP)... (More)
Understanding circuit-level manipulations that affect the brain’s capacity for plasticity will inform the design of targeted interventions that enhance recovery after stroke. Following stroke, increased contralesional activity (e.g. use of the unaffected limb) can negatively influence recovery, but it is unknown which specific neural connections exert this influence, and to what extent increased contralesional activity affects systems-and molecular-level biomarkers of recovery. Here, we combine optogenetic photostimulation with optical intrinsic signal imaging (OISI) to examine how contralesional excitatory activity affects cortical remodeling after stroke in mice. Following photothrombosis of left primary somatosensory forepaw (S1FP) cortex, mice either recovered spontaneously or received chronic optogenetic excitation of right S1FP over the course of 4 weeks. Contralesional excitation suppressed perilesional S1FP remapping and was associated with abnormal patterns of stimulus-evoked activity in the unaffected limb. This maneuver also prevented the restoration of resting-state functional connectivity (RSFC) within the S1FP network, RSFC in several networks functionally-distinct from somatomotor regions, and resulted in persistent limb-use asymmetry. In stimulated mice, perilesional tissue exhibited transcriptional changes in several genes relevant for recovery. Our results suggest that contralesional excitation impedes local and global circuit reconnection through suppression of cortical activity and several neuroplasticity-related genes after stroke, and highlight the importance of site selection for therapeutic intervention after focal ischemia.
(Less)
- author
- organization
- publishing date
- 2022-06
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- functional recovery, optogenetics, Plasticity, resting state functional connectivity, stroke
- in
- eLife
- volume
- 11
- article number
- e68852
- publisher
- eLife Sciences Publications
- external identifiers
-
- scopus:85133832105
- pmid:35723585
- ISSN
- 2050-084X
- DOI
- 10.7554/eLife.68852
- language
- English
- LU publication?
- yes
- id
- 4074614b-eb1d-44ec-8169-30a1e0ad303e
- date added to LUP
- 2022-09-30 13:26:33
- date last changed
- 2024-06-09 18:11:09
@article{4074614b-eb1d-44ec-8169-30a1e0ad303e,
abstract = {{<p>Understanding circuit-level manipulations that affect the brain’s capacity for plasticity will inform the design of targeted interventions that enhance recovery after stroke. Following stroke, increased contralesional activity (e.g. use of the unaffected limb) can negatively influence recovery, but it is unknown which specific neural connections exert this influence, and to what extent increased contralesional activity affects systems-and molecular-level biomarkers of recovery. Here, we combine optogenetic photostimulation with optical intrinsic signal imaging (OISI) to examine how contralesional excitatory activity affects cortical remodeling after stroke in mice. Following photothrombosis of left primary somatosensory forepaw (S1FP) cortex, mice either recovered spontaneously or received chronic optogenetic excitation of right S1FP over the course of 4 weeks. Contralesional excitation suppressed perilesional S1FP remapping and was associated with abnormal patterns of stimulus-evoked activity in the unaffected limb. This maneuver also prevented the restoration of resting-state functional connectivity (RSFC) within the S1FP network, RSFC in several networks functionally-distinct from somatomotor regions, and resulted in persistent limb-use asymmetry. In stimulated mice, perilesional tissue exhibited transcriptional changes in several genes relevant for recovery. Our results suggest that contralesional excitation impedes local and global circuit reconnection through suppression of cortical activity and several neuroplasticity-related genes after stroke, and highlight the importance of site selection for therapeutic intervention after focal ischemia.</p>}},
author = {{Bice, Annie R. and Xiao, Qingli and Kong, Justin and Yan, Ping and Rosenthal, Zachary P. and Kraft, Andrew W. and Smith, Karen and Wieloch, Tadeusz and Lee, Jin Moo and Culver, Joseph P. and Bauer, Adam Q.}},
issn = {{2050-084X}},
keywords = {{functional recovery; optogenetics; Plasticity; resting state functional connectivity; stroke}},
language = {{eng}},
publisher = {{eLife Sciences Publications}},
series = {{eLife}},
title = {{Homotopic contralesional excitation suppresses spontaneous circuit repair and global network reconnections following ischemic stroke}},
url = {{http://dx.doi.org/10.7554/eLife.68852}},
doi = {{10.7554/eLife.68852}},
volume = {{11}},
year = {{2022}},
}