title: Optogenetic mapping after stroke reveals network-wide scaling of functional connections and heterogeneous recovery of the peri-infarct.
abstract: We used arbitrary point channelrhodopsin-2 (ChR2) stimulation and wide-scale voltage sensitive dye (VSD) imaging in mice to map altered cortical connectivity at 1 and 8 weeks after a targeted cortical stroke. Network analysis based on optogenetic stimulation revealed a symmetrical sham network with distinct sensorimotor and association groupings. This symmetry was disrupted after stroke: at 1 week after stroke, we observed a widespread depression of optogenetically evoked activity that extended to the non-injured hemisphere; by 8 weeks, significant recovery was observed. When we considered the network as a whole, scaling the ChR2-evoked VSD responses from the stroke groups to match the sham group mean resulted in a relative distribution of responses that was indistinguishable from the sham group, suggesting network-wide down-scaling and connectional diaschisis after stroke. Closer inspection revealed that connections that had little connectivity with the peri-infarct, such as contralateral visual areas, tended to escape damage, whereas some connections near the peri-infarct were more severely affected. When connections within the peri-infarct were isolated, we did not observe equal down-scaling of responses after stroke. Peri-infarct sites that had weak connection strength in the sham condition tended to have the greatest relative post-stroke recovery. Our findings suggest that, during recovery, most cortical areas undergo homeostatic upscaling, resulting in a relative distribution of responses that is similar to the pre-stroke (sham) network, albeit still depressed. However, recovery within the peri-infarct zone is heterogeneous and these cortical points do not follow the recovery scaling factor expected for the entire network.
authors.affiliation: Department of Psychiatry and.
authors.forename: Diana H
authors.initials: DH
authors.lastname: Lim
authors.affiliation: Department of Psychiatry and Brain Research Center, University of British Columbia at Vancouver, Vancouver V6T 1Z3, Canada.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: LeDue
authors.affiliation: Department of Psychiatry and.
authors.forename: Majid H
authors.identifier: http://orcid.org/0000-0003-0964-2977
authors.initials: MH
authors.lastname: Mohajerani
authors.affiliation: Department of Psychiatry and Brain Research Center, University of British Columbia at Vancouver, Vancouver V6T 1Z3, Canada thmurphy@mail.ubc.ca.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000502:physiology*; D002544:Cerebral Infarction / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D062308:Optogenetics; D010775:Photic Stimulation; D020127:Recovery of Function / Q000502:physiology*
keywords: diachisis; functional recovery; ischemia; optogenetic mapping; plasticity