<scp>L</scp>ocalization of the cannabinoid type‐1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus
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Bibliographic record
Abstract
Abstract Astroglial type‐1 cannabinoid (CB 1 ) receptors are involved in synaptic transmission, plasticity and behavior by interfering with the so‐called tripartite synapse formed by pre‐ and post‐synaptic neuronal elements and surrounding astrocyte processes. However, little is known concerning the subcellular distribution of astroglial CB 1 receptors. In particular, brain CB 1 receptors are mostly localized at cells' plasmalemma, but recent evidence indicates their functional presence in mitochondrial membranes. Whether CB 1 receptors are present in astroglial mitochondria has remained unknown. To investigate this issue, we included conditional knock‐out mice lacking astroglial CB 1 receptor expression specifically in glial fibrillary acidic protein (GFAP)‐containing astrocytes (GFAP‐ CB 1 ‐KO mice) and also generated genetic rescue mice to re‐express CB 1 receptors exclusively in astrocytes (GFAP‐ CB 1 ‐RS). To better identify astroglial structures by immunoelectron microscopy, global CB 1 knock‐out ( CB 1 ‐KO) mice and wild‐type ( CB 1 ‐WT) littermates were intra‐hippocampally injected with an adeno‐associated virus expressing humanized renilla green fluorescent protein (hrGFP) under the control of human GFAP promoter to generate GFAPhrGFP‐ CB 1 ‐KO and ‐WT mice, respectively. Furthermore, double immunogold (for CB 1 ) and immunoperoxidase (for GFAP or hrGFP) revealed that CB 1 receptors are present in astroglial mitochondria from different hippocampal regions of CB 1 ‐WT, GFAP‐ CB 1 ‐RS and GFAPhrGFP‐ CB 1 ‐WT mice. Only non‐specific gold particles were detected in mouse hippocampi lacking CB 1 receptors. Altogether, we demonstrated the existence of a precise molecular architecture of the CB 1 receptor in astrocytes that will have to be taken into account in evaluating the functional activity of cannabinergic signaling at the tripartite synapse.
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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 | 0.001 |
| 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 it