Adrenergic Receptors Modulate Motoneuron Excitability, Sensory Synaptic Transmission and Muscle Spasms After Chronic Spinal Cord Injury
Bibliographic record
Abstract
The brain stem provides most of the noradrenaline (NA) present in the spinal cord, which functions to both increase spinal motoneuron excitability and inhibit sensory afferent transmission to motoneurons (excitatory postsynaptic potentials; EPSPs). NA increases motoneuron excitability by facilitating calcium-mediated persistent inward currents (Ca PICs) that are crucial for sustained motoneuron firing. Spinal cord transection eliminates most NA and accordingly causes an immediate loss of PICs and emergence of exaggerated EPSPs. However, with time PICs recover, and thus the exaggerated EPSPs can then readily trigger these PICs, which in turn produce muscle spasms. Here we examined the contribution of adrenergic receptors to spasms in chronic spinal rats. Selective activation of the α(1A) adrenergic receptor with the agonists methoxamine or A61603 facilitated Ca PIC and spasm activity, recorded both in vivo and in vitro. In contrast, the α(2) receptor agonists clonidine and UK14303 did not facilitate Ca PICs, but did decrease the EPSPs that trigger spasms. Moreover, in the absence of agonists, spasms recorded in vivo were inhibited by the α(1) receptor antagonists WB4010, prazosin, and REC15/2739, and increased by the α(2) receptor antagonist RX821001, suggesting that both adrenergic receptors were endogenously active. In contrast, spasm activity recorded in the isolated in vitro cord was inhibited only by the α(1) antagonists that block constitutive receptor activity (activity in the absence of NA; inverse agonists, WB4010 and prazosin) and not by the neutral antagonist REC15/2739, which only blocks conventional NA-mediated receptor activity. RX821001 had no effect in vitro even though it is an α(2) receptor inverse agonist. Our results suggest that after chronic spinal cord injury Ca PICs and spasms are facilitated, in part, by constitutive activity in α(1) adrenergic receptors. Additionally, peripherally derived NA (or similar ligand) activates both α(1) and α(2) adrenergic receptors, controlling PICs and EPSPs, respectively.
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How this classification was reachedexpand
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".