Glioma-Induced Alterations in Neuronal Activity and Neurovascular Coupling during Disease Progression

Diffusely infiltrating gliomas are known to cause alterations in cortical function, vascular disruption, and seizures. These neurological complications present major clinical challenges, yet their underlying mechanisms and causal relationships to disease progression are poorly characterized. Here, we follow glioma progression in awake Thy1-GCaMP6f mice using in vivo wide-field optical mapping to monitor alterations in both neuronal activity and functional hemodynamics. The bilateral synchrony of spontaneous neuronal activity gradually decreases in glioma-infiltrated cortical regions, while neurovascular coupling becomes progressively disrupted compared to uninvolved cortex. Over time, mice develop diverse patterns of high amplitude discharges and eventually generalized seizures that appear to originate at the tumors’ infiltrative margins. Interictal and seizure events exhibit positive neurovascular coupling in uninfiltrated cortex; however, glioma-infiltrated regions exhibit disrupted hemodynamic responses driving seizure-evoked hypoxia. These results reveal a landscape of complex physiological interactions occurring during glioma progression and present new opportunities for exploring novel biomarkers and therapeutic targets. [Display omitted] •Glioma disrupts neural synchrony between bilateral cortical regions•Tumor development is accompanied by local changes in neurovascular coupling•Wide-field GCaMP imaging reveals glioma-induced interictal discharges and seizures•Altered neurovascular coupling drives hypoperfusion of the tumor during seizures The glioma microenvironment involves multiple cell types. Montgomery et al. utilize in vivo wide-field cortical imaging in awake mice to characterize both neuronal activity and hemodynamics during glioma progression. Observed tumor-localized alterations in neuronal synchrony and neurovascular coupling, interictal events, and seizures reveal potential functional contributions to glioma progression.