Abstract
Axonal plasticity allows neurons to control their output, which critically determines the flow of information in the brain. Axon diameter can be regulated by activity, yet how morphological changes in an axon impact its function remains poorly understood. Axonal swellings have been found on Purkinje cell axons in the cerebellum both in healthy development and in neurodegenerative diseases, and computational models predicts that axonal swellings impair axonal function. Here we report that in young Purkinje cells, axons with swellings propagated action potentials with higher fidelity than those without, and that axonal swellings form when axonal failures are high. Furthermore, we observed that healthy young adult mice with more axonal swellings learn better on cerebellar-related tasks than mice with fewer swellings. Our findings suggest that axonal swellings underlie a form of axonal plasticity that optimizes the fidelity of action potential propagation in axons, resulting in enhanced learning.
| Original language | English |
|---|---|
| Article number | 4129 |
| Journal | Nature Communications |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 5 Jul 2021 |
Bibliographical note
Funding Information:We thank S. du Lac and M. Häusser for generously providing the mice, which originated in the du Lac lab. We thank J. Sjöström for custom software for action potential failure analysis, E. Ruthazer, R. A. McKinney, J. Sjöström, and A. Fournier for thoughtful input on the project, and comments from D. Jaarsma. We thank members of the Watt lab (past and present) for input, support, and feedback on the project and the manuscript as well as N. Recio and A. Huang for technical contribution. We thank Claire Brown and other members of the McGill University Life Sciences Complex Advanced BioImaging Facility (ABIF) and Jackie Vogel and other members of the McGill University Integrated Quantitative Biology Initiative (IQBI) for technical resources and support with X-clarity, lightsheet, and confocal imaging and image analysis. We thank the members of the McGill University Facility for Electron Microscopy Research (FEMR) for technical assistance with TEM. We thank members of the McGill GCC animal care facility for technical assistance, and L. Post and S. Sahin for technical contributions to the VOR data. This work was supported by a Postgraduate PGS-D Scholarship-Doctoral (D.L.-O.) and Summer Undergraduate Research Awards (C.H.L. and C.R.) from the National Science and Engineering Research Council of Canada (NSERC), a McGill Integrated Program in Neuroscience (IPN) Returning Student Award (C.A.S.), and a New Investigator (Nou- veau Chercheur) Grant from the Fonds de Recherche Nature et Technologies de Quebec (A.J.W., 189153), a European Research Council grant (M.S., ERC-Stg No. 680235), a Canadian Institutes of Health Research (CIHR) Operating Grant (A.J.W., 130570) and Project Grant (A.J.W., 153150), an NSERC Discovery Grant (A.J.W., 05118), and a Canadian Foundation for Innovation (CFI) Leaders Opportunity Fund (A.J.W., 29127).
Publisher Copyright:
© 2021, The Author(s).