Neuro-Glioblastoma Connectivity: Brain-Wide Mapping and Cholinergic Modulation of Tumor Progression

This study explores the effect of long-range cholinergic input on glioblastoma (GBM) progression based on systematically mapping neuron-glioma connectivity via monosynaptic rabies virus tracing. To address the mechanism of cholinergic and glutamate inputs lead to increased GBM cell proliferation, we examined transcriptomic changes in patient-derived GBM cells at both early (3h) and chronic (24h) time points following brief exposure to glutamate, Cev, or their combination. Overall design: Patient-derived GBM cells were exposed to vehicle, Cev (10 µM), a selective CHRM1/CHRM3 agonist, glutamate (Glu, 10 µM), or to a combination of Cev and Glu for 1-hour. Then, GBM cells were washed and replaced with fresh medium until lysis for sequencing at different time points. Total RNA was extracted from GBM cells at both early (3h) and chronic (24h) time points for bulk RNA-seq.