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Uncrossed cortical and thalamic circuits to mediate sensory processing weeks after stroke Aminoltejari, Khatereh


One of the enduring principles in neurobiology is that most sensory activity is processed in the hemisphere opposite (contralateral) to the sensation. After a relatively small stroke, function can re-map to related peri-infarct cortical areas. However, after a large stroke, areas with spared and related function may only be present within the “unaffected” hemisphere leading to ipsilateral (un-crossed) sensory processing. We investigated the mechanism of the ipsilateral cortical representation of tactile information before, and 1 and 8-10 weeks after stroke using voltage sensitive dye imaging of forelimb-evoked sensory responses in mice. In control animals before stroke, we observed bilateral cortical activation in response to unilateral stimulation. Ipsilateral forelimb responses before stroke were dependent on the contralateral cortex and presumably mediated through transcallosal fibers that homotopically connect the somatosensory cortices. Large strokes that affected both sensory and motor cortices led to a shift in processing of forelimb sensory stimuli to predominantly the unaffected hemisphere. Pharmacological silencing of the peri-infarct cortex or thalamus within the stroke-affected hemisphere failed to affect prominent non-crossed responses in animals 8-10 weeks after stroke, yet these treatments blocked ipsilateral responses in control animals. Ipsilateral forelimb responses after 8-10 weeks of recovery from a large stroke were attributed to non-crossed ascending circuits that were dependent on the ipsilateral thalamus and apparently substitute for damaged transcallosal cortico-cortical connections. These results indicate that ipsilateral sensory responses present in animals after 8-10 weeks of recovery from stroke are through a fundamentally different mechanism that involves circuits well upstream of the peri-infarct tissue with little dependence on the thalamus or cortex within the stroke-affected hemisphere.

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