Altered excitability of dI3 neurons regulates hindlimb motor tone and locomotor recovery after spinal cord injury
Bibliographic record
Abstract
ABSTRACT Recovery of motor function after spinal cord injury is limited in mammals. Reactivation of locomotor circuits does occur, but primarily through the activation of sensorimotor pathways in the context of locomotor training. Previous investigations have shown that dI3 neurons, a developmentally-defined population of pre-motor, glutamatergic interneurons, are indispensable for this process. However, it remains unclear how dI3 neurons are recruited during locomotor recovery, and whether they could be leveraged to improve locomotor function following spinal cord injury. Herein, we investigated how the excitability of dI3 neurons influences locomotor behaviour and recovery after spinal cord injury. In T9-T10 transected mice, we found that acute chemogenetic silencing of dI3 neurons leads to immediate loss of hindlimb motor tone, and significant reduction in stepping during treadmill locomotion. Conversely, regular chemogenetic stimulation of dI3 neurons led to transient increases in hindlimb motor tone early after injury, but ultimately reduced hindlimb motor tone and locomotor recovery over the long term. These chronic changes resulting from dI3 neuron stimulation were associated with the absence of expression of the constitutive 5-HT2C-R isoform, potentially representing a homeostatic mechanism for the regulation of dI3 excitability following spinal cord injury. Given these findings, we hypothesized that dI3 stimulation’s effects on motor tone, while insufficient to drive locomotor function alone, may promote stepping improvements when locomotor rhythm-generating circuits are active. The addition of quipazine, a serotonergic agonist known to facilitate locomotor rhythmogenesis, in combination with dI3 stimulation, significantly improved locomotor function, while also mitigating the long-term reduction in treadmill stepping associated with dI3 stimulation alone. In aggregate, our results suggest that hyper-excitable dI3 neurons are involved in the maintenance of motor tone after spinal cord injury, possibly through a 5-HT2C-R-dependent mechanism, and further show that the selective stimulation of dI3 neurons could enhance the recovery of locomotor function following spinal cord injury.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".