Formation of somatosensory detour circuits mediates functional recovery following dorsal column injury

Charlène Granier,Evangelia Fourli,Alexandru A. Hennrich,Fabian Laage-Gaupp,Marta Wesolowski,Karl Klaus Conzelmann,Anja Schmalz,Julian Schwarting,Florence M. Bareyre,Anne Jacobi

doi:10.1038/s41598-020-67866-x

Abstract

Anatomically incomplete spinal cord injuries can be followed by functional recovery mediated, in part, by the formation of intraspinal detour circuits. Here, we show that adult mice recover tactile and proprioceptive function following a unilateral dorsal column lesion. We therefore investigated the basis of this recovery and focused on the plasticity of the dorsal column-medial lemniscus pathway. We show that ascending dorsal root ganglion (DRG) axons branch in the spinal grey matter and substantially increase the number of these collaterals following injury. These sensory fibers exhibit synapsin-positive varicosities, indicating their integration into spinal networks. Using a monosynaptic circuit tracing with rabies viruses injected into the cuneate nucleus, we show the presence of spinal cord neurons that provide a detour pathway to the original target area of DRG axons. Notably the number of contacts between DRG collaterals and those spinal neurons increases by more than 300% after injury. We then characterized these interneurons and showed that the lesion triggers a remodeling of the connectivity pattern. Finally, using re-lesion experiments after initial remodeling of connections, we show that these detour circuits are responsible for the recovery of tactile and proprioceptive function. Taken together our study reveals that detour circuits represent a common blueprint for axonal rewiring after injury.

Highlights

Incomplete spinal cord injuries can be followed by functional recovery mediated, in part, by the formation of intraspinal detour circuits
We show that sensory afferents originating from cervical dorsal root ganglion (DRG) remodel following spinal cord injury by first increasing the number of axon collaterals that enter the grey matter and second by increasing their contacts onto spinal relay neurons that provide a detour connection to the corresponding brain stem center
Following an unilateral dorsal column lesion, we could observe a significant increase in the number of collaterals emerging from ipsilateral DRG axons caudal to the lesion e.g. between the segments cervical level 2 (C2) to C6 (Fig. 2b,c)

Summary

Introduction

Incomplete spinal cord injuries can be followed by functional recovery mediated, in part, by the formation of intraspinal detour circuits. In the motor system it is well-established that the re-wiring of neuronal circuits is the structural basis for functional recovery of the damaged central nervous system (CNS)[1,2,3,4,5] For this detour circuit to form, corticospinal tract (CST) projection neurons first extend new collaterals into the grey matter, where they make new synaptic contacts with different populations of intraspinal relay neurons. We show that sensory afferents originating from cervical DRGs remodel following spinal cord injury by first increasing the number of axon collaterals that enter the grey matter and second by increasing their contacts onto spinal relay neurons that provide a detour connection to the corresponding brain stem center. Our work demonstrates that the formation of intraspinal detour circuits occurs in the motor system and in the sensory system, and likely represent a conserved strategy that mediates functional restoration of brain-spinal connectivity

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Results

Conclusion