Corticospinal neurons respond differentially to neurotrophins and myelin‐associated glycoprotein in vitro
Bibliographic record
Abstract
Elucidating the mechanisms that regulate the survival and outgrowth of corticospinal tract (CST) neurons and other CNS tracts will be a key component in developing novel approaches for the treatment of central nervous system (CNS) disorders, including stroke, spinal cord injury (SCI), and motor neuron disease (MND). However, the in vivo complexities of these diseases make a systematic evaluation of potential therapeutics that directly affect corticospinal regeneration or survival very challenging. Here, we use Thy1.2 transgenic mice expressing yellow fluorescent protein (YFP) in postnatal day 8 (P8) corticospinal neurons, as a source of CST neurons that have already established synapses in the spinal cord, to assess factors that influence neurite outgrowth and survival of axotomized CST neurons. After culture, YFP-positive corticospinal neurons represent an enriched neuronal population over other glia and interneurons, survive, and extend processes over time. YFP-positive CST neurons also continue to express the corticospinal markers CTIP2 and Otx1. CST neurons display different degrees of axon extension, dendritic branch length and elaboration, and neurite elongation in response to neurotrophin-3 and ciliary neurotrophic factor, and an inhibitory outgrowth response when cultured on myelin-associated glycoprotein. Some CST neurons are lost with extended culture, which provides a baseline from which we can also assess factors that enhance CST neuron survival. This assay thus allows us to assess independent aspects of CST axonal and dendritic outgrowth kinetics, which allows for the rapid and sensitive investigation of new therapies to address corticospinal neuron outgrowth in the context of CNS injury and neurodegenerative disorders.
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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 | 0.008 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 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".