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Myelin, an insulating sheath, wraps axonal segments to facilitate signal propagation and when deficient, can impair visual function. Optic nerve development and initial myelination has largely been considered completed by the fifth postnatal week. However, the relationship between the extent of myelination and axonal signaling in the maturing optic nerve is not well characterized. Here, we examine the relationship between axon conduction and elements of myelination using extracellular nerve recordings, immunohistochemistry, western blot analysis, scanning electron microscopy, and simulations of nerve responses. Comparing compound action potentials from mice aged 4\u201312\u00a0weeks revealed five functional distinct axonal populations, an increase in the number of functional axons, and shifts toward fast\u2010conducting axon populations at 5 and 8\u00a0weeks postnatal. At these ages, our analysis revealed increased myelin thickness, lower g\u2010ratios and changes in the 14\u00a0kDa MBP isoform, while the density of axons and nodes of Ranvier remained constant. At 5 postnatal weeks, axon diameter increased, while at 8\u00a0weeks, increased expression of a mature sodium ion channel subtype, Na<jats:sub>v<\/jats:sub> 1.6, was observed at nodes of Ranvier. A simulation model of nerve conduction suggests that ion channel subtype, axon diameter, and myelin thickness are more likely to be key regulators of nerve function than g\u2010ratio. Such refinement of axonal function and myelin rearrangement identified an extended period of maturation in the normal optic nerve that may facilitate the development of visual signaling patterns.<\/jats:p>","DOI":"10.1002\/dneu.22875","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T07:58:33Z","timestamp":1649663913000},"page":"308-325","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Refinement of axonal conduction and myelination in the mouse optic nerve indicate an extended period of postnatal developmental plasticity"],"prefix":"10.1002","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0681-1862","authenticated-orcid":false,"given":"Annika","family":"Balraj","sequence":"first","affiliation":[{"name":"Department of Anatomy The George Washington University School of Medicine and Health Sciences  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Clarkson\u2010Paredes","sequence":"additional","affiliation":[{"name":"Nanofabrication and Imaging Center The George Washington University School of Medicine and Health Sciences  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahdeah","family":"Pajoohesh\u2010Ganji","sequence":"additional","affiliation":[{"name":"Department of Anatomy The George Washington University School of Medicine and Health Sciences  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew W.","family":"Kay","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The George Washington University  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mendelowitz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology The George Washington University School of Medicine and Health Sciences  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Anatomy The George Washington University School of Medicine and Health Sciences  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00637.2005"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-11-04388.1999"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.23329"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087736"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22060"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1516"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00265-3"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01184071"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0051-17.2017"},{"key":"e_1_2_9_11_1","unstructured":"Dangata Y. 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