Persistent extrasynaptic hyperdopaminergia in the mouse hippocampus induces plasticity and recognition memory deficits reversed by the atypical antipsychotic sulpiride
Bibliographic record
Abstract
Evidence suggests that subcortical hyperdopaminergia alters cognitive function in schizophrenia and antipsychotic drugs (APD) fail at rescuing cognitive deficits in patients. In a previous study, we showed that blocking D2 dopamine receptors (D2R), a core action of APD, led to profound reshaping of mesohippocampal fibers, deficits in synaptic transmission and impairments in learning and memory in the mouse hippocampus (HP). However, it is currently unknown how excessive dopamine affects HP-related cognitive functions, and how APD would impact HP functions in such a state. After verifying the presence of DAT-positive neuronal projections in the ventral (temporal), but not in the dorsal (septal), part of the HP, GBR12935, a blocker of dopamine transporter (DAT), was infused in the CA1 of adult C57Bl/6 mice to produce local hyperdopaminergia. Chronic GBR12935 infusion in temporal CA1 induced a mild learning impairment in the Morris Water Maze and abolished long-term recognition memory in novel-object (NORT) and object-place recognition tasks (OPRT). Deficits were accompanied by a significant decrease in DAT+ mesohippocampal fibers. Intrahippocampal or systemic treatment with sulpiride during GBR infusions improved the NORT deficit but not that of OPRT. In vitro application of GBR on hippocampal slices abolished long-term depression (LTD) of fEPSP in temporal CA1. LTD was rescued by co-application with sulpiride. In conclusion, chronic DAT blockade in temporal CA1 profoundly altered mesohippocampal modulation of hippocampal functions. Contrary to previous observations in normodopaminergic mice, antagonising D2Rs was beneficial for cognitive functions in the context of hippocampal hyperdopaminergia.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.002 |
| 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".