title: Dynamic Modulation of Myelination in Response to Visual Stimuli Alters Optic Nerve Conduction Velocity.
abstract: Myelin controls the time required for an action potential to travel from the neuronal soma to the axon terminal, defining the temporal manner in which information is processed within the CNS. The presence of myelin, the internodal length, and the thickness of the myelin sheath are powerful structural factors that control the velocity and fidelity of action potential transmission. Emerging evidence indicates that myelination is sensitive to environmental experience and neuronal activity. Activity-dependent modulation of myelination can dynamically alter action potential conduction properties but direct functional in vivo evidence and characterization of the underlying myelin changes is lacking. We demonstrate that in mice long-term monocular deprivation increases oligodendrogenesis in the retinogeniculate pathway but shortens myelin internode lengths without affecting other structural properties of myelinated fibers. We also demonstrate that genetically attenuating synaptic glutamate neurotransmission from retinal ganglion cells phenocopies the changes observed after monocular deprivation, suggesting that glutamate may constitute a signal for myelin length regulation. Importantly, we demonstrate that visual deprivation and shortened internodes are associated with a significant reduction in nerve conduction velocity in the optic nerve. Our results reveal the importance of sensory input in the building of myelinated fibers and suggest that this activity-dependent alteration of myelination is important for modifying the conductive properties of brain circuits in response to environmental experience.
  
  
  
  Oligodendrocyte precursor cells differentiate into mature oligodendrocytes and are capable of ensheathing axons with myelin without molecular cues from neurons. However, this default myelination process can be modulated by changes in neuronal activity. Here, we show, for the first time, that experience-dependent activity modifies the length of myelin internodes along axons altering action potential conduction velocity. Such a mechanism would allow for variations in conduction velocities that provide a degree of plasticity in accordance to environmental needs. It will be important in future work to investigate how these changes in myelination and conduction velocity contribute to signal integration in postsynaptic neurons and circuit function.
authors.affiliation: Department of Neurology, University of California, San Francisco, California 94158.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Etxeberria
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, California 94143, and Program in Neuroscience, University of California, San Francisco, California 94158.
authors.forename: Kenton C
authors.identifier: 0000-0003-2514-0432
authors.initials: KC
authors.lastname: Hokanson
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, California 94143, and.
authors.forename: Dang Q
authors.initials: DQ
authors.lastname: Dao
authors.affiliation: Department of Neurology, University of California, San Francisco, California 94158.
authors.forename: Sonia R
authors.initials: SR
authors.lastname: Mayoral
authors.affiliation: Department of Neurology, University of California, San Francisco, California 94158.
authors.forename: Feng
authors.identifier: 0000-0003-4075-6841
authors.initials: F
authors.lastname: Mei
authors.affiliation: Department of Neurology, University of California, San Francisco, California 94158, Program in Neuroscience, University of California, San Francisco, California 94158.
authors.forename: Stephanie A
authors.identifier: 0000-0002-5580-6269
authors.initials: SA
authors.lastname: Redmond
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, California 94143, and Program in Neuroscience, University of California, San Francisco, California 94158.
authors.forename: Erik M
authors.identifier: 0000-0003-2077-8584
authors.initials: EM
authors.lastname: Ullian
authors.affiliation: Department of Neurology, University of California, San Francisco, California 94158, Program in Neuroscience, University of California, San Francisco, California 94158 jonah.chan@ucsf.edu.
authors.forename: Jonah R
authors.identifier: 0000-0002-2176-1242
authors.initials: JR
authors.lastname: Chan
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D002772:Cholera Toxin / Q000378:metabolism; D005829:Geniculate Bodies / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000502:physiology* / Q000648:ultrastructure; D009431:Neural Conduction / Q000235:genetics / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology* / Q000648:ultrastructure; D038081:Organogenesis / Q000235:genetics / Q000502:physiology; D010775:Photic Stimulation; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics / Q000378:metabolism; D015349:Vision, Monocular / Q000502:physiology*; D014795:Visual Pathways / Q000502:physiology* / Q000648:ultrastructure; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D002772:Cholera Toxin; D060850:LIM-Homeodomain Proteins; D011509:Proteoglycans; D014157:Transcription Factors; D050599:Vesicular Glutamate Transport Protein 2; D000099216:Chondroitin Sulfate Proteoglycan 4; C493477:Slc17a6 protein, mouse; C063843:insulin gene enhancer binding protein Isl-1
keywords: conduction velocity; glutamate; monocular deprivation; myelin; oligodendrocyte; optic nerve