NMNAT proteins that limit Wallerian degeneration also regulate critical period plasticity in the visual cortex

Mariska Van Lier, Laura Smit-Rigter, Roos Krimpenfort, M. Hadi Saiepour, Emma Ruimschotel, Willem Kamphuis, J. Alexander Heime, Christiaan N. Levelt*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Many brain regions go through critical periods of development during which plasticity is enhanced. These critical periods are associated with extensive growth and retraction of thalamocortical and intracortical axons. Here, we investigated whether a signaling pathway that is central in Wallerian axon degeneration also regulates critical period plasticity in the primary visual cortex (V1). Wallerian degeneration is characterized by rapid disintegration of axons once they are separated from the cell body. This degenerative process is initiated by reduced presence of cytoplasmic nicotinamide mononucleotide adenylyltransferases (NMNATs) and is strongly delayed in mice overexpressing cytoplasmic NMNAT proteins, such as Wld S mutant mice producing a UBE4b-NMNAT1 fusion protein or NMNAT3 transgenic mice. Here, we provide evidence that in Wld S mice and NMNAT3 transgenic mice, ocular dominance (OD) plasticity in the developing visual cortex is reduced. This deficit is only observed during the second half of the critical period. Additionally, we detect an early increase of visual acuity in the V1 of Wld S mice. We do not find evidence for Wallerian degeneration occurring during OD plasticity. Our findings suggest that NMNATs do not only regulate Wallerian degeneration during pathological conditions but also control cellular events that mediate critical period plasticity during the physiological development of the cortex.

Original languageEnglish
Article numbere0277-18.2018
Pages (from-to)1-12
Number of pages12
Issue number1
Publication statusPublished - 4 Jan 2019


This work was supported through a grant from AgentschapNL to the NeuroBasic PharmaPhenomics consortium, The Netherlands Organisation for Scientific Research (NWO) Grant 823.02.001, a grant from Stichting Blindenhulp, a donation from Praktijkgenerator b.v., and a Vidi grant (to J.A.H.).

FundersFunder number
Neu-roBasic PharmaPhenomics consortium
Nederlandse Organisatie voor Wetenschappelijk Onderzoek823.02.001
Stichting Blindenhulp


    • Axon
    • Cortex
    • Critical period
    • Plasticity
    • Wallerian degeneration


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