Aberrant cortical activity, functional connectivity, and neural assembly architecture after photothrombotic stroke in mice

Abstract

AbstractDespite substantial recent progress in mapping the trajectory of network plasticity resulting from focal ischemic stroke, there is mixed evidence for changes in neuronal excitability and activity within the peri-infarct cortex of mice. Most of these data have been acquired from anesthetized animals, acute tissue slices, or immunoassays on extracted tissue, and thus may not reflect cortical activity dynamics in the intact cortex of an awake animal. Here,in vivotwo- photon calcium imaging in awake, behaving mice was used to longitudinally track cortical activity, network functional connectivity, and neural assembly architecture for 2 months following photothrombotic stroke targeting the forelimb somatosensory cortex. This model is associated with sensorimotor recovery over the weeks following stroke, allowing us to relate network changes to behavior. Our data revealed spatially restricted but long-lasting alterations in somatosensory neural networks. Specifically, we demonstrate significant and long-lasting disruptions in neural assembly architecture concurrent with a deficit in functional connectivity between individual neurons. Reductions in neuronal spiking in peri-infarct cortex were transient but predictive of impairment in skilled locomotion measured in the tapered beam task. Notably, altered neural networks were highly localized, with assembly architecture and neural connectivity relatively unaltered a distance outside the peri-infarct cortex, even in regions demonstrated to be the site of functional remapping of the forelimb somatosensory representation in anaesthetized preparations. Thus, using longitudinal two photon microscopy in awake animals, these data show a complex spatiotemporal relationship between peri-infarct neuronal network function and behavioral recovery that is more nuanced than functional remapping in response to strong sensory stimulation under anesthesia.