Differential regulation of NMDAR and NMDAR‐mediated metaplasticity by anandamide and 2‐AG in the hippocampus
Bibliographic record
Abstract
Endocannabinoids (eCBs), including AEA and 2-AG, are endogenous signaling mediators involved in many physiological and pathological events. The G protein-coupled cannabinoid receptor 1 (CB1 R) is an important target for eCBs, however, additional non-CB1 receptor targets have also been identified. Although recent evidence suggests that NMDA receptor function may be regulated by eCBs, the underlying mechanisms remain poorly characterized. Using acutely isolated CA1 neurons and slices from the hippocampus, we found that both AEA and 2-AG potentiate NMDAR-mediated currents independently of CB1 receptors (CB1 Rs) and via distinct signaling pathways. Potentiation by AEA requires the activation of TRPV1 channels. In contrast, potentiation by 2-AG requires the sequential activation of PKC and Src. Additionally, in hippocampal slices, we found that both AEA and 2-AG induce NMDAR-mediated metaplasticity and facilitate the induction of subsequent LTD independently of CB1 Rs. Enhanced LTD by AEA, but not 2-AG, was dependent on TRPV1 channels. Our findings reveal previously unrecognized non-CB1 R-dependent signaling cascades through which the two major eCBs regulate NMDA receptor function and consequently synaptic plasticity.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 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".