Cervical neurons control locomotion
Bibliographic record
Abstract
The locomotor neural network consisting of genetically defined interneuronal populations is primarily located in the ventromedial region of the lumbar enlargement. Long direct reticulospinal projections have shown to be critical for the activation of this lumbar locomotor network. While, much less is known about the functional connectivity of the cervical propriospinal input during overground locomotion. Here, we first prove that the cervical neurons constitute a major excitatory pathway to locomotor areas of the lumbar spinal cord. Further, we found that cervical spondylotic myelopathy (CSM), the most common form of spinal cord injury selectively disrupts the cervical propriospinal input, and not the reticulospinal, to the lumbar locomotor network. This finding was associated with specific loss of glutamatergic neurons in the rhythmogenic segments of lumbar cord and subsequent decrease in cadence, speed and mobility during overground locomotion. The gradual loss of speed and cadence over time with intact reticulospinal tracts and early disruption of the cervical excitatory monosynaptic input onto excitatory lumbar neurons early in CSM indicate an important role of specific cervico–lumbar pathway in locomotion. To further prove this, we initially ablated the lumbar projecting cervical neurons in naïve mice by employing a dual‐injection experiment. Gait analysis during overground locomotion demonstrated that ablation of these neurons resulted in progressively decreased speed and cadence compared to controls. These neurobehavioural results closely mirrored the locomotion deficits seen in severe human and mice CSM. In addition and similar to the neuroanatomical changes noticed in the severe CSM, stereological analysis demonstrated a decreased number of neurons in the lumbar enlargement of the AAV‐DTA treated animals compared to controls. To further confirm the role of lumbar projecting cervical neurons in initiating and maintaining locomotion, we next selectively silenced the lumbar‐projecting cervical neurons using TeLC. Overtime, TeLC treated animals demonstrated decreased locomotor speed, cadence and overall mobility compared to controls. This phenotype was characterized by a significant increase in the inactive time and decrease in the mobile time and mobile counts compared to control mice indicative of a perturbed ability to initiate and maintain mobility. TeLC‐mediated silencing closely reproduced the locomotor phenotype of CSM and DTA treated animals.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".