Laminar and sex- specific expression of GluN2A, GluN2B and GluN2D NMDA receptor subunits within the dorsal horn of male and female rat spinal cord
Bibliographic record
Abstract
N-methyl-D-aspartate receptors (NMDARs) are excitatory ionotropic glutamate receptors expressed throughout the central nervous system (CNS), including in the dorsal horn (DH) of the spinal cord. The GluN2 subunits of NMDARs, GluN2A, 2B and 2D, confer NMDARs with structural and functional variability, enabling heterogeneity in synaptic transmission and plasticity. Despite essential roles for NMDARs in physiological and pathological pain processing within the DH, the distribution and function of specific GluN2 isoforms across DH laminae remains poorly understood. Furthermore, surprisingly, GluN2 expression in female rodents has been completely overlooked. We therefore investigated the relative expression of specific GluN2 variants in the L4/L5 lumbar DH of both male and female rats. With the aim to detect also the synaptic GluN2 isoforms that are expressed in the DH (GluN2A, 2B and 2D), we used pepsin antigen-retrieval to unmask these highly cross-linking protein complexes. We discovered that GluN2B and GluN2D were preferentially localized to superficial regions of the DH in males, while only GluN2B was predominantly expressed in the superficial DH of female rats. Moreover, unexpectedly, we identified an elevated expression of GluN2B in the medial division versus the lateral division of the superficial DH, in males only. These sex-specific localization patterns of GluN2-NMDAR subunits have significant implications for the understanding and treatment of pain and are relevant for future translational studies in human spinal cord tissue.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.007 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| 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 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".