Longitudinal monitoring of mesoscopic cortical activity in a mousemodel of microinfarcts reveals dissociations with behavioral and motorfunction

摘要

Small vessel disease is characterized by sporadic obstruction of small vesselsleading to neuronal cell death. These microinfarcts often escape detection byconventional magnetic resonance imaging and are identified only upon postmortemexamination. Our work explores a brain-wide microinfarct model in awakehead-fixed mice, where occlusions of small penetrating arterioles are reproducedby endovascular injection of fluorescent microspheres. Mesoscopic functionalconnectivity was mapped longitudinally in awake GCaMP6 mice using geneticallyencoded calcium indicators for transcranial wide-field calcium imaging.Microsphere occlusions were quantified and changes in cerebral blood flow weremeasured with laser speckle imaging. The neurodeficit score in microinfarct micewas significantly higher than in sham, indicating impairment in motor function.The novel object recognition test showed a reduction in the discrimination indexin microinfarct mice compared to sham. Graph-theoretic analysis of functionalconnectivity did not reveal significant differences in functional connectivitybetween sham and microinfarct mice. While behavioral tasks revealed impairmentsfollowing microinfarct induction, the absence of measurable functionalalterations in cortical activity has a less straightforward interpretation. Thebehavioral alterations produced by this model are consistent with alterationsobserved in human patients suffering from microinfarcts and support the validityof microsphere injection as a microinfarct model.