Uld allow the change of node length to be accommodated without a change of internode length, and furthermore node length might change by an eversion of the paranodal loops closest to the node without any other significant change to the myelin sheath (reviewed by Arancibia-Carcamo and Attwell, 2014). Thus, small changes in nodal length might well occur without major remodelling of the myelin sheath. Nevertheless, if one assumes that node shortening by X mm absolutely does require an X mm elongation of the myelin sheath, then more membrane changes are needed than are accounted for in our simple calculation. One can show mathematically that the sheath membrane area increase is larger than the area decrease at the node by a factor of 2x(number of myelin wraps)x(mean radius of wraps)/(node radius), which is roughly 18.4 for the optic nerve and 13 for the cortex. Accounting for these area changes (and noting that, in this situation, there is no change of total axon length) would reduce the ratio of the membrane area changes needed to produce a given speed change (when adding a layer of myelin to the sheath versus changing the node length) from 1006-fold to 55-fold for the optic nerve and from 273fold to 21-fold for the cortex, but these ratios remain impressively large, and so the energetic argument favouring speed tuning by alteration of the node length still holds.StatisticsData are shown as mean .e.m. Comparisons are via 2-tailed Student’s t-tests unless otherwise stated. Assessment of whether the slope of linear regressions differed significantly from zero was obtained using the t-statistic for the slope.AcknowledgementsSupported by a Wellcome Trust Senior Investigator Award to DA, a Wellcome Trust PhD studentship to LC, a Marie Curie fellowship to MCF, and JSPS grants (24650181 and 25245069) to KT.Zilovertamab We thank Boris Barbour, Beverley Clark, Renaud Jolivet, Josef Kittler, Anna Krasnow and Angus Silver for comments on the manuscript.Additional informationFundingFunder Wellcome Trust Grant reference number 099222/Z/12/Z Author I Lorena Arancibia-Carcamo Lee Cossell David Attwell Marc C Ford Kinji Ishida Koujiro Tohyama Kinji Ishida Koujiro TohyamaEuropean Commission Japan Society for the Promotion of Science London Japan Society for the Promotion of Science London623714 AxonGliaPlasticity 24650181Arancibia-Carcamo et al.Ebastine eLife 2017;6:e23329. DOI: 10.7554/eLife.23329 12 ofResearch article The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.PMID:25818744 NeuroscienceAuthor contributions ILA-C, Conceptualization, Data curation, Software, Formal analysis, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing–original draft, Writing–review and editing; MCF, Conceptualization, Data curation, Formal analysis, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing–original draft, Writing–review and editing; LC, Conceptualization, Resources, Data curation, Software, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing–original draft, Writing–review and editing; KI, Investigation, Visualization, Methodology; KT, DA, Conceptualization, Resources, Data curation, Software, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing–original draft, Project administration, Writing–review and editing Author ORCIDs Marc C Ford, http://orcid.org/0000-0003.