Distinguishing subtypes of spinal locomotor neurons to inform circuit function and dysfunction

Dougherty, Kimberly J.

doi:10.1016/j.conb.2023.102763

Cited by 8 publications

(11 citation statements)

References 69 publications

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“…Given the variety of functions performed by the spinal cord and the diversity of interneurons involved [100][101][102] , combination treatments are likely to be critical to locomotor recovery following SCI. Previous studies using AAV-BDNF or ES have largely focused on motor neuron physiology and have indirectly characterized changes occurring at the interneuronal level through changes in neurotransmitter expression patterns [23][24][25]103 .…”

Section: Deep Dorsal Inhibitory Rorβ Excitability Correlates With Fun...mentioning

confidence: 99%

Activity of spinal RORβ neurons is related to functional improvements following combination treatment after complete SCI

Stachowski,

Wheel,

Atoche

et al. 2024

Preprint

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Various strategies targeting spinal locomotor circuitry have been associated with functional improvements after spinal cord injury (SCI). However, the neuronal populations mediating beneficial effects remain largely unknown. In a mouse model of complete SCI, virally-delivered BDNF (AAV-BDNF) activates hindlimb stepping and causes hyperreflexia, whereas sub-motor threshold epidural stimulation (ES) reduced BDNF-induced hyperreflexia. Given their role in gating proprioceptive afferents and potential convergence point of BDNF and ES, we hypothesized that an enhanced excitability of inhibitory RORβ neurons would be associated with locomotor improvements. Ex vivo spinal slice recordings revealed that the excitability of RORβ neurons was decreased in mice with poor locomotor function after SCI, but was similar between the uninjured and 'best stepping' SCI groups. Further, chemogenetic excitation of RORβ neurons reduced BDNF-induced hyperreflexia and improved stepping, similar to ES. Our findings identify inhibitory RORβ neurons as a target population to limit hyperreflexia and enhance locomotor function after SCI.

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Section: Deep Dorsal Inhibitory Rorβ Excitability Correlates With Fun...mentioning

confidence: 99%

Activity of spinal RORβ neurons is related to functional improvements following combination treatment after complete SCI

Stachowski,

Wheel,

Atoche

et al. 2024

Preprint

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“…Premotor INs can be primarily classified following general neuronal features such as where they project (ipsilateral, if they project to the same hemicord where their soma is located, or commissural, when they cross the midline), if their axon is contained in the same spinal segment or they send their prolongations to other spinal levels (short or long), which neurotransmitter(s) they release (excitatory or inhibitory), and their firing properties [12,15,31,32]. However, there is still no consensus about the best way to group different subsets of INs in a meaningful manner to be able to study them separately, as well as to describe the interrelations among them, in the adult ventral spinal cord [25,33,34]. At present, the most used classification has been the cardinal system, in which cardinal cell populations are named according to their progenitor cells and the expression of specific transcription factors during the early embryological stages [35].…”

Section: Current Challenges To Characterize Spinal Premotor Interneur...mentioning

confidence: 99%

“…In this review, we will focus on the premotor INs contained in motor circuits and how they react after different kinds of TSCI. For a broader information about the spinal circuitry responsible for the locomotion in the ventral spinal cord and central pattern generators, the authors strongly recommend reviewing the indicated publications [23][24][25][26][27][28]. neurons (MNs), which receive inputs from supraspinal centers and sensory afferents (in a direct or indirect way) and send their output to muscles and premotor interneurons (INs).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Potential Roles of Specific Subclasses of Premotor Interneurons in Spinal Cord Function Recovery after Traumatic Spinal Cord Injury in Adults

Dominguez-Bajo,

Clotman

2024

Cells

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The differential expression of transcription factors during embryonic development has been selected as the main feature to define the specific subclasses of spinal interneurons. However, recent studies based on single-cell RNA sequencing and transcriptomic experiments suggest that this approach might not be appropriate in the adult spinal cord, where interneurons show overlapping expression profiles, especially in the ventral region. This constitutes a major challenge for the identification and direct targeting of specific populations that could be involved in locomotor recovery after a traumatic spinal cord injury in adults. Current experimental therapies, including electrical stimulation, training, pharmacological treatments, or cell implantation, that have resulted in improvements in locomotor behavior rely on the modulation of the activity and connectivity of interneurons located in the surroundings of the lesion core for the formation of detour circuits. However, very few publications clarify the specific identity of these cells. In this work, we review the studies where premotor interneurons were able to create new intraspinal circuits after different kinds of traumatic spinal cord injury, highlighting the difficulties encountered by researchers, to classify these populations.

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“…Physiological and pathological perturbations affect the ability of animals to coordinate their body during the execution of locomotion, significantly affecting intra-and interlimb coordination (Grillner et al 2020). Many labs have identified pathologies in humans and animal models (Boyer et al, 2017;Dougherty, 2023;Stolze et al, 2000;Zanardi et al 2021) causing locomotor dysfunctions, yet the customised analysis algorithms, the selected parameters chosen, and the different ways to normalise step-cycle phases render it difficult to compare these results and correlate, for example, walk impairments in rodent models and human patients having the same mutation or pathology. Thus, establishing a tool for the automated analysis of locomotion will enable the standardised comparison across experimental groups, species, and laboratories, allowing the identification of conserved principles of motor control and adaptation.…”

Section: Introductionmentioning

confidence: 99%

AutoGaitA – Automated Gait Analysis in Python

Hosseini,

Klein,

Kuzu

et al. 2024

Preprint

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Animals change their location in space by means of walking, running, swimming, or flying, a series of rhythmic motor behaviours that together are defined as locomotion. Individual types of locomotion require a unique coordinated pattern of muscle contractions that can be inferred by the location of joints across the body. Implementations of recent advancements in machine learning (ML), such as DeepLabCut and Simi Shape, have automated the tracking of body posture, even in markerless subjects. Despite ML algorithms alleviating the tracking effort, making sense of the tracked points still requires substantial amounts of manual labour and lacks standardisation across research labs. To this end, we developed AutoGaitA (Automated Gait Analysis), an open-source Python toolbox designed to automate the analysis of locomotion by normalising the step cycle, extracting meaningful features from the tracked coordinates (e.g. angles, velocity, acceleration) and allowing intra- and inter-animal comparisons. Here, we employed AutoGaitA in a series of proof of principles experiments to show age-dependent changes in locomotion in flies, mice and humans, age-dependent changes in adaptation mechanisms in mice, and to compare the key features of walking across species. AutoGaitA's adaptability to any kind of motor behaviour and any species of interest makes it a valuable tool for the motor community to standardise the analysis of rhythmic behaviours across genotypes, disease states and species.

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Distinguishing subtypes of spinal locomotor neurons to inform circuit function and dysfunction

Cited by 8 publications

References 69 publications

Activity of spinal RORβ neurons is related to functional improvements following combination treatment after complete SCI

Activity of spinal RORβ neurons is related to functional improvements following combination treatment after complete SCI

Potential Roles of Specific Subclasses of Premotor Interneurons in Spinal Cord Function Recovery after Traumatic Spinal Cord Injury in Adults

AutoGaitA – Automated Gait Analysis in Python

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