are not depleted under normal conditions. However, it is not known whether this dynamic is altered in response to demyelinating lesions. Neuron-OPC interactions Node of Ranvier OPCs extend their processes to the nodes of Ranvier and together with astrocyte processes make up the nodal glial complex. Since the nodes of Ranvier contain a high density of voltage-dependent sodium channels and allow regenerative action potentials to be generated, it is speculated that this location allows OPCs to sense and possibly respond to neuronal activity Neuromodulation OPCs synthesize the neuromodulatory factors prostaglandin D2 synthase (PTGDS) and neuronal pentraxin 2 (NPTX2). This is regulated by NG2, whose intracellular domain can be cleaved by γ-secretase and translocated to the nucleus. The NG2 ectodomain can also modulate AMPA and NMDA receptor-dependent LTP. Constitutive and activity-dependent cleavage of NG2 by ADAM10 releases the ectodomain, which contains two N-terminal LNS domains that act on neuronal synapses. Neuron-OPC synapse OPCs express numerous voltage-gated ion channels and neurotransmitter receptors. Structural studies have shown that neurons form synapses with OPCs in both gray matter and white matter. Electron microscopy revealed OPC membranes apposed to neuronal presynaptic terminals filled with synaptic vesicles. OPCs express AMPA receptors and GABAA receptors and undergo small membrane depolarizations in response to presynaptic vesicular glutamate or GABA release. OPCs can undergo cell division while maintaining synaptic inputs from neurons. These observations suggest that cells that receive neuronal synaptic inputs and those that differentiate into oligodendrocytes are not mutually exclusive cell populations but that the same population of OPCs can receive synaptic inputs and generate myelinating oligodendrocytes. However, OPCs appear to lose their ability to respond to synaptic inputs from neurons as they differentiate into mature oligodendrocytes. The functional significance of the neuron-OPC synapses remains to be elucidated. Immunomodulation OPCs may participate in both initiation and resolution of immune responses to disease or injury. They are highly responsive to injury, undergo a morphological activation similar to that of astrocytes and microglia, and may contribute to glial scar formation. Conversely, OPCs have been shown to downregulate microglia activation and protect against neuronal death. They also express and secrete many immune-related molecules, such as chemokines, cytokines, interleukins, and other related ligands or receptors. Recent work has illustrated that OPCs can act as antigen presenting cells via both MHC class I and class II and can activate both CD4+ and CD8+ T cells. Clinical significance Transplantation of OPCs has been