Dual Regulation of Anterograde and Retrograde Transmission by Endocannabinoids
Bibliographic record
Abstract
Endocannabinoids (eCBs) are feedback messengers in the nervous system that act at the presynaptic nerve terminal to inhibit transmitter release. Here we report that in brain slices from rat, eCBs are released from vasopressin (VP) neurons in the paraventricular nucleus of the hypothalamus following coincident bursts of presynaptic and postsynaptic spiking. eCBs transiently depress glutamate release from excitatory terminals and, in doing so, prevent the synapses from undergoing long-term depression (LTD). Specifically, we show that blockade of CB1 receptors unmasks LTD following coincident presynaptic and postsynaptic activity. This LTD is presynaptic in nature, but requires the release of the opioid peptide dynorphin from the postsynaptic neuron. Dynorphin release and subsequent LTD require the activation of postsynaptic metabotropic glutamate receptors (mGluRs). Our findings indicate that eCBs, by transiently depressing glutamate release, limit mGluR activation and indirectly gate release of dynorphin from the postsynaptic neuron. We propose that eCBs, in addition to their well described role in the rapid modulation of transmitter release from the nerve terminal, also regulate the release of other retrograde transmitters and thus encode for multiple temporal windows of synaptic plasticity.
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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) | 0.000 | 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 | 0.001 |
| 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".