title: Rapid Mechanically Controlled Rewiring of Neuronal Circuits.
abstract: CNS injury may lead to permanent functional deficits because it is still not possible to regenerate axons over long distances and accurately reconnect them with an appropriate target. Using rat neurons, microtools, and nanotools, we show that new, functional neurites can be created and precisely positioned to directly (re)wire neuronal networks. We show that an adhesive contact made onto an axon or dendrite can be pulled to initiate a new neurite that can be mechanically guided to form new synapses at up to 0.8 mm distance in <1 h. Our findings challenge current understanding of the limits of neuronal growth and have direct implications for the development of new therapies and surgical techniques to achieve functional regeneration. Significance statement: Brain and spinal cord injury may lead to permanent disability and death because it is still not possible to regenerate neurons over long distances and accurately reconnect them with an appropriate target. Using microtools and nanotools we have developed a new method to rapidly initiate, elongate, and precisely connect new functional neuronal circuits over long distances. The extension rates achieved are ≥60 times faster than previously reported. Our findings have direct implications for the development of new therapies and surgical techniques to achieve functional regeneration after trauma and in neurodegenerative diseases. It also opens the door for the direct wiring of robust brain-machine interfaces as well as for investigations of fundamental aspects of neuronal signal processing and neuronal function.
authors.affiliation: Department of Physics, McGill University, Montreal, Quebec H3A 2T8, Canada, Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Magdesian
authors.affiliation: Department of Physics, McGill University, Montreal, Quebec H3A 2T8, Canada.
authors.forename: G Monserratt
authors.initials: GM
authors.lastname: Lopez-Ayon
authors.affiliation: Department of Physics, McGill University, Montreal, Quebec H3A 2T8, Canada.
authors.forename: Megumi
authors.identifier: http://orcid.org/0000-0002-4810-5480
authors.initials: M
authors.lastname: Mori
authors.affiliation: Institut Universitaire en Santé Mentale de Québec, Quebec, Quebec G1J 2G3, Canada, Department of Psychiatry and Neuroscience, Université Laval, Quebec, Quebec G1V 0A6, Canada.
authors.forename: Dominic
authors.initials: D
authors.lastname: Boudreau
authors.affiliation: Department of Chemistry, McGill University, Montreal, Quebec H3A 2K6, Canada, and.
authors.forename: Alexis
authors.identifier: http://orcid.org/0000-0003-1382-532X
authors.initials: A
authors.lastname: Goulet-Hanssens
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Sanz
authors.affiliation: Department of Physics, McGill University, Montreal, Quebec H3A 2T8, Canada.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Miyahara
authors.affiliation: Institut Universitaire en Santé Mentale de Québec, Quebec, Quebec G1J 2G3, Canada, Department of Psychiatry and Neuroscience, Université Laval, Quebec, Quebec G1V 0A6, Canada.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Barrett
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Alyson E
authors.identifier: http://orcid.org/0000-0002-1859-7015
authors.initials: AE
authors.lastname: Fournier
authors.affiliation: Institut Universitaire en Santé Mentale de Québec, Quebec, Quebec G1J 2G3, Canada, Department of Psychiatry and Neuroscience, Université Laval, Quebec, Quebec G1V 0A6, Canada, Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3A 1Y6, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: De Koninck
authors.affiliation: Department of Physics, McGill University, Montreal, Quebec H3A 2T8, Canada, peter.grutter@mcgill.ca.
authors.forename: Peter
authors.identifier: http://orcid.org/0000-0003-1719-8239
authors.initials: P
authors.lastname: Grütter
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D008297:Male; D009415:Nerve Net / Q000166:cytology / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
keywords: atomic force microscopy; axonal growth; electrophysiology; neurodegenerative disease; neuronal networks; neuronal regeneration