AMPA receptors and seizures mediate hippocampal radial glia‐like stem cell proliferation
Bibliographic record
Abstract
Neurogenesis is sustained throughout life in the mammalian brain, supporting hippocampus-dependent learning and memory. Its permanent alteration by status epilepticus (SE) is associated with learning and cognitive impairments. The mechanisms underlying the initiation of altered neurogenesis after SE are not understood. Glial fibrillary acidic protein-positive radial glia (RG)-like cells proliferate early after SE, but their proliferation dynamics and signaling are largely unclear. We have previously reported a polarized distribution of AMPA receptors (AMPARs) on RG-like cells in vivo and postulated that these may signal their proliferation. Here, we examined the acute effects of kainate on hippocampal precursor cells in vitro and in kainate-induced SE on proliferating and quiescent clones of 5-bromo-2-deoxyuridine prelabeled hippocampal precursors in vivo. In vitro, we found that 5 μM kainate shortened the cell cycle time of RG-like cells via AMPAR activation and accelerated cell cycle re-entry of their progeny. It also shifted their fate choice expanding the population of RG-like cells and reducing the population of downstream amplifying neural progenitors. Kainate enhanced the survival of all precursor cell subtypes. Pharmacologically, kainate's proliferative and survival effects were abolished by AMPAR blockade. Functional AMPAR expression was confirmed on RG-like cells in vitro. In agreement with these observations, kainate/seizures enhanced the proliferation and expansion predominantly of constitutively cycling RG-like cell clones in vivo. Our results identify AMPARs as key potential players in initiating the proliferation of dentate RG-like cells and unravel a possible receptor target for modifying the radial glia-like cell response to SE.
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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 | 0.000 |
| 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".