title: Endogenous GABA controls oligodendrocyte lineage cell number, myelination, and CNS internode length.
abstract: Adjusting the thickness and internodal length of the myelin sheath is a mechanism for tuning the conduction velocity of axons to match computational needs. Interactions between oligodendrocyte precursor cells (OPCs) and developing axons regulate the formation of myelin around axons. We now show, using organotypic cerebral cortex slices from mice expressing eGFP in Sox10-positive oligodendrocytes, that endogenously released GABA, acting on GABAAreceptors, greatly reduces the number of oligodendrocyte lineage cells. The decrease in oligodendrocyte number correlates with a reduction in the amount of myelination but also an increase in internode length, a parameter previously thought to be set by the axon diameter or to be a property intrinsic to oligodendrocytes. Importantly, while TTX block of neuronal activity had no effect on oligodendrocyte lineage cell number when applied alone, it was able to completely abolish the effect of blocking GABAAreceptors, suggesting that control of myelination by endogenous GABA may require a permissive factor to be released from axons. In contrast, block of AMPA/KA receptors had no effect on oligodendrocyte lineage cell number or myelination. These results imply that, during development, GABA can act as a local environmental cue to control myelination and thus influence the conduction velocity of action potentials within the CNS. GLIA 2017;65:309-321.
authors: Department of Neuroscience, Pharmacology and Physiology, University College London, London, WC1E 6BT, United Kingdom.
authors: Nicola B
authors: NB
authors: Hamilton
authors: Department of Neuroscience, Pharmacology and Physiology, University College London, London, WC1E 6BT, United Kingdom.
authors: Laura E
authors: LE
authors: Clarke
authors: Department of Neuroscience, Pharmacology and Physiology, University College London, London, WC1E 6BT, United Kingdom.
authors: I Lorena
authors: IL
authors: Arancibia-Carcamo
authors: Department of Cell and Developmental Biology, Wolfson Institute for Biomedical Research, University College London, London, WC1E 6BT, United Kingdom.
authors: Eleni
authors: E
authors: Kougioumtzidou
authors: Wellcome Trust-MRC Cambridge Stem Cell Institute, Cambridge, CB2 1QR, United Kingdom.
authors: Moritz
authors: M
authors: Matthey
authors: Wellcome Trust-MRC Cambridge Stem Cell Institute, Cambridge, CB2 1QR, United Kingdom.
authors: Ragnhildur
authors: R
authors: Káradóttir
authors: Department of Neuroscience, Pharmacology and Physiology, University College London, London, WC1E 6BT, United Kingdom.
authors: Louise
authors: L
authors: Whiteley
authors: Department of Oral Biology, Brain and Muscle Energy Group, University of Oslo, Blindern, Oslo, N-0317, Norway.|Department of Anatomy, University of Oslo, Blindern, Oslo, N-0317, Norway.
authors: Linda H
authors: LH
authors: Bergersen
authors: Department of Cell and Developmental Biology, Wolfson Institute for Biomedical Research, University College London, London, WC1E 6BT, United Kingdom.
authors: William D
authors: WD
authors: Richardson
authors: Department of Neuroscience, Pharmacology and Physiology, University College London, London, WC1E 6BT, United Kingdom.
authors: David
authors: D
authors: Attwell
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology* / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D038081:Organogenesis / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018682:GABA Agents; D011810:Quinoxalines; D018079:Receptors, GABA; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid
keywords: GABA; internode; myelination; oligodendrocyte; precursor; proliferation