Role of Persistent Sodium and Calcium Currents in Motoneuron Firing and Spasticity in Chronic Spinal Rats
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Bibliographic record
Abstract
After chronic spinal injury, motoneurons spontaneously develop two persistent inward currents (PICs): a TTX-sensitive persistent sodium current (sodium PIC) and a nimodipine-sensitive persistent calcium current (calcium PIC). In the present paper, we examined how these PICs contributed to motoneuron firing. Adult rats were spinalized at the S(2) sacral level, and after 2 months intracellular recordings were made from sacrocaudal motoneurons in vitro. The PICs and repetitive firing were measured with slow triangular voltage and current ramps, respectively. The sodium PIC was examined after blocking the calcium PIC with nimodipine (20 microM; n = 12). It was always activated subthreshold, and during current ramps in nimodipine, it produced a sodium plateau that assisted in initiating and maintaining firing (self-sustained firing). The sodium PIC oscillated off and on during firing and helped initiate each spike, and near threshold this caused abnormally slow firing (2.82 +/- 1.21 Hz). A low dose of TTX (0.5 microM) blocked the sodium PIC, sodium plateau, and very slow firing prior to affecting the spike itself. The calcium PIC was estimated as the current blocked by nimodipine or current remaining in TTX (2 microM; n = 13). In 59% of motoneurons, the calcium PIC was activated subthreshold to firing and produced a plateau that assisted in initiating and sustaining firing because nimodipine significantly increased the firing threshold current and decreased the self-sustained firing. In the remaining motoneurons (41%), the calcium PIC was activated suprathreshold to firing and during current ramps did not initially affect firing but eventually was activated and caused an acceleration in firing followed by self-sustained firing, which were blocked by nimodipine. The frequency-current (F-I) slope was 3.0 +/- 1.0 Hz/nA before the calcium PIC activation (primary range), 6.3 +/- 3.6 Hz/nA during the calcium PIC onset (secondary range; acceleration), and 2.1 +/- 1.3 Hz/nA with the calcium PIC steadily activated (tertiary range). Nimodipine eliminated the secondary and tertiary ranges, leaving a linear F-I slope of 3.7 +/- 1.0 Hz/nA. A single low-threshold shock to the dorsal root evoked a many-second-long discharge, the counterpart of a muscle spasm in the awake chronic spinal rat. This long-lasting reflex was caused by the motoneuron PICs because when the activation of the voltage-dependent PICs was prevented by hyperpolarization, the same dorsal root stimulation only produced a brief excitatory postsynaptic potential (<1 s). Both the calcium and sodium PIC were involved because nimodipine only partly reduced the reflex and there remained very slow firing mediated by the sodium PIC.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 it