UBC Theses and Dissertations
Spatially resolving acute functional changes in descending cortical motor output after targeted stroke Anenberg, Eitan
We evaluated the effects of mini-strokes targeted to individual pial arterioles on motor and cortical function within the first hours after ischemia. This was done in Thy-1 line 18 channelrhodopsin-2 (ChR2) transgenic mice. Using optogenetics, we directly assessed both the excitability and motor output of cortical neurons in a rapid, repeated, and relatively non-invasive manner independent of behavioral state or training. Occlusion of individual arterioles within the motor cortex led to a ministroke that was verified using laser speckle contrast imaging. Surprisingly, ministrokes targeted to a relatively small region of the forelimb motor map, with an ischemic core of 0.07 ± 0.03 mm², impaired motor responses evoked from points across widespread areas of motor cortex even 1.5 mm away. Contrasting averaged ChR2-evoked electroencephalographic, spinal (ChR2 evoked potential), and electromyographic responses revealed a mismatch between measures of cortical excitability and motor output within 60 min after stroke. This mismatch suggests that apparently excitable cortical neurons (even >1 mm into peri-infarct areas, away from the infarct core) were impaired in their capacity to generate spinal potentials leading to even more severe deficits in motor output at muscles. We suggest that ischemia, targeted to a subset of motor cortex, leads to relatively small reductions in excitability within motor cortex, and cumulative depression of both descending spinal circuits and motor output in response to the activation of widespread cortical territories even outside of the area directly affected by the ischemia.
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