Abstract 132: Chronic Optogenetic Stimulation of Thalamocortical Projections Promotes Axonal Rewiring and Accelerates Recovery of Function After Somatosensory Cortex Stroke
Bibliographic record
Abstract
The majority of stroke survivors must cope with chronic disability of the limbs. Improved limb use is generally accompanied by neuroplasticity in surviving brain areas surrounding the stroke. Modulating this innate plasticity should promote further gains in recovery. One relatively unknown issue in stroke research concerns the role of the thalamus, the brain’s relay center for sensory information en route to the cortex. Unpublished data from our lab has shown that while peri-infarct thalamocortical axons are relatively resilient to the effects of ischemia, they are highly unstable and lose a significant number of synaptic boutons in the first few weeks after stroke. We now expand on this by hypothesizing that optogenetic stimulation of peri-infarct thalamocortical projections will promote axonal rewiring and improve recovery from somatosensory cortex stroke. Axons projecting from the VPL nucleus of the thalamus to primary forelimb somatosensory cortex were co-transfected with a fluorescently tagged adeno-associated virus that expressed channelrhodopsin-2 and mCherry. A chronic cranial window was then implanted to allow for longitudinal in vivo two-photon imaging of superficial thalamic axon terminals before and at various times after photothrombotic stroke. Optogenetic stimulation was driven by a blue LED (475 nm, 6-10mW/mm2) magnetically attached to the cranial window. Optical stimulation (5 ms pulses at 5 Hz every 5 seconds) or control procedures were initiated 3 days after stroke in freely moving mice for 1 hour/day, 5 days/week for 6 weeks after stroke. Behavioural performance on the Tape Removal Test and Ladder Walking Test were assessed once weekly throughout the entire recovery period. Preliminary data show that optogenetic stimulation of thalamocortical projections is associated with an attenuated period of thalamocortical bouton elimination, increased bouton formation and greater stability/persistence of newly formed boutons. Importantly, stimulated mice showed less severe forepaw deficits and faster recovery of sensorimotor function. These studies offer encouraging new insights into the application of optogenetic approaches for improving stroke recovery.
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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) | 0.000 | 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) | 0.005 | 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".