Abstract 158: Optogenetic Theta-band Activation of Pyramidal Neurons Elicits Peri-infarct Spreading Depolarizations in the ET-1 Rat Model of Focal Cortical Ischemia
Bibliographic record
Abstract
Peri-infarct spreading depolarization (PIDs) frequently occur post ischemic stroke in animals and humans, propagating from the infarct core into the penumbra, and have been associated with worsened neurological outcome in patients. The etiology of PIDs is not well understood, complicating the development of targeted treatments. To examine the cellular origins of PIDs, we hypothesized that synchronous, frequency-specific, activation of specific neuronal subpopulation is necessary for PID occurrence. We transfected adult male Sprague Dawley rats with ChR2 either under the CamKII (AAV5.CAMKII.ArchT.GFP.WPRE.SV40) or CAG (AAV5.CAG.hChR2(H134R)-mCherry.WPRE.SV40) promoters into the somatosensory cortex to induce opsin transfection in pyramidal neurons or interneurons, respectively. Two weeks later, we assessed neuronal activity changes induced by focal cortical ischemia by inserting two electrodes ~2 mm apart in rostro-caudal direction. We then used a glass micropipette to inject 800 pmol of ET-1 into the primary somatosensory cortex in correspondence of rostral electrode, so as to examine the activity at the ‘core’ of the ischemic insult as well as from the peri-infarct zone, which coincided with the transfected area. We recorded baseline (pre-ischemic) local field potentials (LFPs) before injecting ET-1. Following ET-1 injection, we observed an average of five CSDs, with a mean amplitude of 57 mV and a mean duration of 1.2min, propagating from the infarct core to the peri-infarct tissue. In all subjects, the CSDs subsided within the first hour after the ischemic insult. In the second hour following stroke, we stimulated peri-infarct pyramidal neurons or interneurons at different frequency bands (theta, alpha, beta, low gamma, high gamma, and DC). Only theta band stimulation of the pyramidal neurons reliably triggered PIDs. Stimulating pyramidal neurons at higher frequencies or interneurons at any frequency did not elicit PIDs. Activation of peri-infarct zone pyramidal neurons in the theta band elicits cortical PIDs. The identification of a neuronal-specific and frequency-specific trigger for PIDs provides a roadmap for development of PID-targeted treatments in the acute stage of stroke.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".