Studying Synaptic Integration of Glioma Cells into Neural Circuits

Nervous system activity regulates homeostasis, development, and plasticity of the brain. Certain glial cell populations regulate neuronal activity by controlling neurotransmitter availability at the synapse or regulating extracellular ion concentrations. Glial precursor cells can give rise to gliomas, which are the leading cause of brain cancer-related death. Recent studies have demonstrated the influence of neuronal activity on the progression of a range of high-grade gliomas. One process through which neurons influence gliomas is the formation of functional bona fide synapses between presynaptic neurons and postsynaptic glioma cells. Here, we present multiple techniques that can be utilized to study these neuron-to-glioma synapses. We present a coculture method for in vitro studies and layout the process for generating patient-derived xenograft models in mice for in vivo and in situ studies. We describe the use of electron microscopy to observe the structural characteristics of synapses and electrophysiological studies to investigate the electrical properties of such synapses. We also outline two-photon calcium imaging as a powerful tool to study network-level consequences of activity-depended currents in glioma cells. While similar questions can be answered using electrophysiology and calcium imaging, electrophysiology is useful for directly probing synaptic responses and membrane potential changes while calcium imaging is useful for studying network-level changes.