Gill Lab

We developed an ex vivo platform to study how gliomas drive seizure activity using acute brain slices from a mouse model of high-grade glioma. By recording electrophysiological signals across tumor, infiltrated, and surrounding brain regions, we found that tumor-bearing tissue showed markedly increased neuronal firing and more frequent seizure-like events compared with controls, particularly under seizure-provoking conditions. These abnormal discharges most often arose at the tumor margins and nearby cortex, highlighting how tumor invasion disrupts local brain networks and promotes epileptiform activity. Together, this work provides new insight into how gliomas alter neural circuitry to generate seizures and establishes a powerful experimental system for studying tumor-associated epilepsy.

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In this study, we used a combination of single-unit recordings and wide-field calcium imaging in an ex vivo brain slice model of diffusely infiltrating glioma to track how different types of neurons behave during seizure-like activity. We found that in tumor-bearing tissue, fast-spiking interneurons fire less, become active primarily during excitatory bursts, and show impaired local inhibition, while overall excitability increases compared with controls. By pharmacologically targeting the system with an mTOR inhibitor, we were able to boost interneuron firing and restore inhibition, which corresponded with reduced overall excitability. These results suggest that glioma can disrupt the balance between excitatory and inhibitory neurons in a way that contributes to hyperexcitability and seizures, and that some of these changes may be reversible with mTOR inhibition.

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We used MRI-guided biopsies from both contrast-enhancing tumor cores and non-enhancing margins of human glioblastoma to compare their molecular and cellular composition. We found that the non-enhancing margins—regions typically left behind after surgical resection and responsible for tumor recurrence—are biologically distinct from the contrast-enhancing core and contain a greater contribution from non-tumor brain cells. When we compared these region-specific profiles across glioblastoma subtypes, contrast-enhancing samples reflected classical molecular signatures, while non-enhancing margins more closely resembled neural tissue. We also observed subtype-specific differences in the proportions of astrocytes, oligodendrocyte progenitors, and microglia at the infiltrative edge. Together, these findings highlight the biological heterogeneity of the tumor margins and underscore the importance of targeting this infiltrative region to improve therapeutic outcomes.

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