Wireless closed-loop optogenetics across the entire dorsoventral spinal cord in mice

Claudia Kathe, Frédéric Michoud, Philipp Schönle, Andreas Rowald, Noé Brun, Jimmy Ravier, Ivan Furfaro, Valentina Paggi, Kyungjin Kim, Sadaf Soloukey, Leonie Asboth, Thomas H. Hutson, Ileana Jelescu, Antoine Philippides, Noaf Alwahab, Jérôme Gandar, Daniel Huber, Chris I. De Zeeuw, Quentin Barraud, Qiuting HuangStéphanie P. Lacour*, Grégoire Courtine*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)

Abstract

Optoelectronic systems can exert precise control over targeted neurons and pathways throughout the brain in untethered animals, but similar technologies for the spinal cord are not well established. In the present study, we describe a system for ultrafast, wireless, closed-loop manipulation of targeted neurons and pathways across the entire dorsoventral spinal cord in untethered mice. We developed a soft stretchable carrier, integrating microscale light-emitting diodes (micro-LEDs), that conforms to the dura mater of the spinal cord. A coating of silicone–phosphor matrix over the micro-LEDs provides mechanical protection and light conversion for compatibility with a large library of opsins. A lightweight, head-mounted, wireless platform powers the micro-LEDs and performs low-latency, on-chip processing of sensed physiological signals to control photostimulation in a closed loop. We use the device to reveal the role of various neuronal subtypes, sensory pathways and supraspinal projections in the control of locomotion in healthy and spinal-cord injured mice.

Original languageEnglish
Pages (from-to)198-208
Number of pages11
JournalNature Biotechnology
Volume40
Issue number2
Early online date27 Sep 2021
DOIs
Publication statusPublished - Feb 2022

Bibliographical note

Funding Information:
We thank B. Schneider for providing viral vectors, and L. Batti and S. Pagès from the ALICe platform for light-sheet imaging. Financial support was provided by a Consolidator Grant from the European Research Council (ERC-2015-CoG HOW2WALKAGAIN 682999), the Swiss National Science Foundation (subsidies 310030_130850, CRSII5_183519, BSCGI0 1578000) and the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant agreement no. 785907 (Human Brain Project SGA2) and the Bertarelli Foundation. C.K. is supported by a Marie Skłodowska-Curie postdoctoral fellowship and HFSP long-term fellowship (LT001278/2017-L). S.S. and C.I.D.Z. are supported by grants from BIG (Erasmus MC), Medical-NeuroDelta and INTENSE (LSH-NWO).

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.

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