The growth of high-grade glioma (HGG) and proliferation of glial precursor cells are enhanced by neuronal activity, but the mechanisms are not known. A new study shows that optogenetic stimulation of cortical neurons in a patient-derived glioblastoma xenograft model in mice increased precursor proliferation. Crucially, a similar effect was obtained by application of conditioned medium from activated neurons to cultured HGG, suggesting that the mitogen responsible was secreted. Indeed, the secreted mitogen was revealed to be neuroligin 3, which, by acting through the phosphatidylinositol 3-kinase–mammalian target of rapamycin pathway, was necessary and sufficient to promote HGG growth.