Functional Local Proprioceptive Feedback Circuits Initiate and Maintain Locomotor Recovery after Spinal Cord Injury
Authors: Silvia Arber
Aya Takeoka
Journal: Cell Reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: locomotion; mouse genetics; neuronal circuit reorganization; proprioception; somatosensory feedback
Affiliations: Neuro-electronics Research Flanders (NERF), 3001 Leuven, Belgium; Vlaams Institute for Biotechnology (VIB), 3001 Leuven, Belgium; Department of Neuroscience and Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium. Electronic address: ., Biozentrum, Department of Cell Biology, University of Basel, 4056 Basel, Switzerland; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland. Electronic address: .

Abstract:  Somatosensory feedback from proprioceptive afferents (PAs) is essential for locomotor recovery after spinal cord injury. To determine where or when proprioception is required for locomotor recovery after injury, we established an intersectional genetic model for PA ablation with spatial and temporal confinement. We found that complete or spatially restricted PA ablation in intact mice differentially affects locomotor performance. Following incomplete spinal cord injury, PA ablation below but not above the lesion severely restricts locomotor recovery and descending circuit reorganization. Furthermore, ablation of PAs after behavioral recovery permanently reverts functional improvements, demonstrating their essential role for maintaining regained locomotor function despite the presence of reorganized descending circuits. In parallel to recovery, PAs undergo reorganization of activity-dependent synaptic connectivity to specific local spinal targets. Our study reveals that PAs interacting with local spinal circuits serve as a continued driving force to initiate and maintain locomotor output after injury. 

Retracted: No

PubPeer comments:
 This is a very interesting paper, making use of novel techniques to confirm the importance of intact proprioception in the recovery following spinal cord injury. Among the many experiments, the authors perform trans-synaptic tracing using their landmark method of muscle injections of the modified SADB19 rabies virus, preceded by spinal injection of a Cre dependent AAV-SADB19-G. It turns out these experiments were performed in adult mice, but this is just briefly commented upon within the paper. I know this is only a small part of the study, but to my knowledge, it is the first example of rabies infection of motoneurons following muscle injections in adult animals. Many labs have tried it without success, so it would be great to know how the authors performed such experiments. Unfortunately, the Methods section does not report any detail, like the volume injected or the titer of the virus. More importantly, it would be extremely useful to have an idea of the efficiency of infection, in terms of raw number of starter motoneurons and of infected premotor interneurons. Such information cannot be inferred from the paper, since premotor interneurons data are only reported as contour plots in Figure 6. I am making this comment public, rather than contacting directly the authors in private, because I think that a response from the authors would be of interest to most people using rabies based tracing from muscles. Marco Beato , 
 I believe this preprint may report an experimental follow-up to the above comment. https: www.biorxiv.org content 10.1101 2021.02.10.430608v1 , 
 #2 Not really. The comment above was a request for further information that cannot be extracted from the published paper, while the linked preprint is a general presentation of the results obtained from rabies tracing using different methods. ,