Fig. 2 |. Neuronal activity-regulated mechanisms of glioma growth.

Neuronal activity drives glioma proliferation, growth and progression through activity-regulated paracrine factors including neuroligin 3 (NLGN3)^11,103,111, brain-derived neurotrophic factor (BDNF)^11,120, insulin-like growth factor 1 (IGF1)¹⁰⁶, activity-regulated increases in potassium (K⁺) that evoke K⁺ currents in glioma cells^12,102 and bona fide neuron-to-glioma synapses^{12,102,120,123}. K⁺-evoked currents are amplified through gap junction coupling between glioma cells via tumour microtubes^12,102. Activity-regulated interactions also induce gene expression changes in glioma cells relevant to multiple aspects of glioma network integration^11,111. In particular, NLGN3 signalling induces glioma gene expression changes that underpin other neuron–glioma interactions, including upregulating synapse-associated genes, the BDNF receptor tyrosine receptor kinase B (TrkB) (NTRK2), the synaptogenic factor thrombospondin 1 (TSP1), genes encoding K⁺ channels, tumour microtube-associated genes including connexin 43 (CX43) (GJA1) and axon guidance genes including semaphorins (implicated in glioma invasion¹⁰⁷)¹¹¹. AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor.