Technical approaches and challenges to study AMPA receptors in oligodendrocyte lineage cells: Past, present, and future

Abstract

Receptors for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPARs) are ligand-gated ionotropic receptors for glutamate that is a major excitatory neurotransmitter in the central nervous system. AMPARs are located at postsynaptic sites of neuronal synapses where they mediate fast synaptic signaling and synaptic plasticity.Remarkably, AMPARs are also expressed by glial cells. Their expression by the oligodendrocyte (OL) lineage cells is of special interest because AMPARs mediate fast synaptic communication between neurons and oligodendrocyte progenitor cells (OPCs), modulate proliferation and differentiation of OPCs, and may also be involved in regulation of myelination. On the other hand, during pathological conditions, AMPARs may mediate damage of the OL lineage cells. In the present review, we focus on the technical approaches that have been used to study AMPARs in the OL lineage cells, and discuss future perspectives of AMPAR research in these glial cells.

Recent Insights into the Functional Role of AMPA Receptors in the Oligodendrocyte Lineage Cells In Vivo

“…However, the effects of neuronal activity on the OL lineage cells may be more complex because it is possible that even the same patterns of neuronal activity influence OPCs and/or OLs in distinct ways, depending on the subunit composition, trafficking and persistence of surface AMPARs at neuron–glia synapses and/or in the myelin. We have recently reviewed several state-of-the-art approaches which have been used for studying AMPARs in neurons and that can be applied to further investigate the properties and functions of AMPARs in OL lineage cells [ 1 ]. It will be especially interesting to study the oligodendroglial AMPARs in freely moving animals and also in combination with behavioural paradigms.…”

“…The OL lineage encompasses cells at different stages of differentiation—from the OL progenitor cells (OPCs) to the myelinating OLs—both in the developing and in the adult brain ( Figure 1 ). It is well established that OPCs (also known as glial cells expressing neural/glial antigen 2, or NG2 + -glia) express functional AMPARs that mediate depolarizing inward current into the cell upon glutamate binding, and we summarized studies relevant to this topic in a recent review [ 1 ]. All four AMPAR subunits have been detected in OPCs, although their expression and properties seem to vary depending on the brain area, age of the animals, and the model system used to investigate the receptors [ 1 ].…”

“…It is well established that OPCs (also known as glial cells expressing neural/glial antigen 2, or NG2 + -glia) express functional AMPARs that mediate depolarizing inward current into the cell upon glutamate binding, and we summarized studies relevant to this topic in a recent review [ 1 ]. All four AMPAR subunits have been detected in OPCs, although their expression and properties seem to vary depending on the brain area, age of the animals, and the model system used to investigate the receptors [ 1 ]. Remarkably, multiple studies demonstrate that, similar to AMPAR-mediated synaptic communication between neurons, AMPAR-mediated synaptic signalling exists between neurons and OPCs in different areas of the rodent and human brain including the white matter [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”