5‐HT<sub>3</sub><sub>A</sub> receptors maintain hippocampal LTP in a CB<sub>1</sub> and GABA<sub>A</sub> receptor‐ dependent manner for spatial memory
Bibliographic record
Abstract
Background and Purpose As the only ionotropic receptor in the 5‐HT receptor family, the 5‐HT 3 receptor (5‐HT 3 R) is involved in psychiatric disorders and its modulators have potential therapeutic effects for cognitive impairment in these disorders. However, it remains unclear how 5‐HT 3 Rs shape synaptic plasticity for memory function. Experimental Approach Extracellular as well as whole‐cell electrophysiological recordings were used to monitor hippocampal LTP and synaptic transmission in hippocampal slices in 5‐HT 3 AR knockout or 5‐HT 3 AR‐GFP mice. Immunocytochemistry, qRT‐PCR and western blotting were used to measure receptor expression. We also assessed hippocampal dependent cognition and memory, using the Morris water maze (MWM) and novel object recognition. Key Results We found that 5‐HT 3 R dysfunction impaired hippocampal LTP in Schaffer collateral (SC)‐CA1 pathway in hippocampal slices, by facilitating GABAergic inputs in pyramidal cells. This effect was dependent on 5‐HT 3 Rs on axon terminals. It resulted from reduced expression and function of the cannabinoid receptor 1 (CB 1 R) co‐localized with 5‐HT 3 Rs on axon terminals, and then led to diminishment of tonic inhibition of GABA release by CB 1 Rs. Inhibition of CB 1 Rs mimicked the facilitation of GABAergic transmission by 5‐HT 3 R disruption. Consequently, mice with hippocampal 5‐HT 3 R disruption exhibited impaired spatial memory in MWM tasks. Conclusion and Implications These results suggest that 5‐HT 3 Rs are crucial in enabling hippocampal synaptic plasticity via a novel CB 1 R‐GABA A ‐dependent pathway to regulate spatial memory.
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 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".