The potential role of nonneuronal cells in the deep brain stimulation mechanism: What are glia? what are their functions? Could they be players in deep brain stimulation?

Deep brain stimulation (DBS) is the surgical therapy of choice for a variety of treatment-resistant movement disorders, and many neuropsychiatric disorders. However, the mode of action of DBS is still unclear. It is unknown which neural cell types in the complex brain circuitry are involved in the workings of DBS, and how high-frequency stimulation of specific cell types may lead to the alleviation of a patient’s clinical symptoms. Although the existing theories of the working of DBS rely mostly on neurons, it is likely that other cell types could be involved. It is known that glia are heavily involved in synaptic communication through the formation of the tripartite synapse. Recent evidence indicates that DBS can result in direct activation of glial cells to release gliotransmitters. This in turn can have an effect on the tripartite synapse, as well as on downstream network activity. In this chapter we focus on reviewing the effects of DBS on nonneuronal cells, and speculate on the potential role of DBS-mediated glial activation.