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J Neurosci. 2014 Dec 3;34(49):16455-66. doi: 10.1523/JNEUROSCI.3384-14.2014.

Optogenetic mapping after stroke reveals network-wide scaling of functional connections and heterogeneous recovery of the peri-infarct.

Author information

1
Department of Psychiatry and.
2
Department of Psychiatry and Brain Research Center, University of British Columbia at Vancouver, Vancouver V6T 1Z3, Canada.
3
Department of Psychiatry and Brain Research Center, University of British Columbia at Vancouver, Vancouver V6T 1Z3, Canada thmurphy@mail.ubc.ca.

Erratum in

  • J Neurosci. 2015 Jun 17;35(24):9247.

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.

KEYWORDS:

diachisis; functional recovery; ischemia; optogenetic mapping; plasticity

PMID:
25471583
DOI:
10.1523/JNEUROSCI.3384-14.2014
[Indexed for MEDLINE]
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