Increased Dopamine Transmission Impairs Behavioral Flexibility and Synaptic Plasticity
Bibliographic record
Abstract
In addition to its key roles in motor and reward systems, brain dopamine (DA) has also been implicated in integrative functions contributing to adaptive behaviors such as attention, learning and memory, which processing involved the plastic changes of synaptic strength. Since the first formal evidence for Long Term Plasticity mechanism (LTP) in the Hippocampal Formation (HF), the phenomenon of synaptic plasticity has been described in various brain areas. It is appealing to consider that this is particularly true for brain regions that receive DA inputs, including the striatum and the frontal cortex being those most studied beside the hippocampus. We have observed, using mice lacking the dopamine transporter (DAT) which constitute a unique genetic model of persistent functional hyperdopaminergia, a strong deficit of LTD and an enhancement of LTP in the CA1 region of hippocampal slices. This finding suggests that the augmentation of endogenous dopamine by DAT knockout modulates the plastic property of bidirectional synaptic plasticity by inducing a metaplastic shift in the HF. This deficit of LTD can be reversed by the D2 antagonist haloperidol, whereas the LTP increase is not altered. In the same animals, we observed a major impairment of cued-learning in the Morris watermaze, as well as more subtle, but solid, deficits in the spatial learning. These deficits of behavioral flexibility are reversed using haloperidol. Finally, in control animals, the direct blockade of the DAT using GBR12935, can reproduce the LTD and the behavioral deficits, indicating that they are not a consequence of developmental changes.
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".