Kougioumtzidou, E; (2015) Regulation of oligodendrocyte development by electrical signalling (N/A,, Trans.). Doctoral thesis , UCL (University College London).

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Abstract

Myelin in the CNS is produced by oligodendrocytes (OLs), which are themselves produced by oligodendrocyte precursors (OLPs). OLPs are generated during embryonic development and continue to proliferate and give rise to new OLs throughout life. OLPs express a number of ion channels and neurotransmitter receptors, and receive synaptic input from neurons. The role of this synaptic communication has remained elusive. In this Thesis I investigated the developmental role of electrical communication between neurons and OLPs. I examined the expression of glutamate receptors of the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic) subclass in cells of the OL lineage. This revealed that OLPs are likely to express three of the four AMPA receptor subunits (GluA2-4). I started to investigate the function of these subunits by generating GluA2/GluA3 single and double knockout mice. This resulted in reduced glutamatergic synaptic signalling to OLPs. The decrease in synaptic input was accompanied by a decrease in the number of OLPs and mature OLs. Thus, glutamatergic synaptic input to OLPs promotes their development. To investigate this question further in the future, I have generated new transgenic mouse lines that should allow manipulation of electrical communication specifically between neurons and OLPs in vivo.

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