MODULATION OF THE L-TYPE CALCIUM CHANNEL CAV1.2 BY NOCICEPTIN AND ITS RECEPTOR NOP1
Bibliographic record
Abstract
The endogenous neuropeptide nociceptin (N/OFQ) and its receptor, the nociceptin receptor (NOP1), are highly expressed in the hippocampus, where they regulate learning and memory by inhibiting synaptic transmission and plasticity. The L-type calcium channel (LTCC) Cav1.2 is also expressed in the hippocampus and is one of the major sources of Ca 2+ in the postsynaptic compartment of neurons. Activation of Cav1.2 regulates memory and learning-associated biochemical changes through activation of cAMP response element-binding protein (CREB) and NMDA receptor-independent long-term potentiation (LTP). It has previously been shown that activation of NOP1 receptor by nociceptin downregulates LTCCs as well as other voltage gated calcium channels in hippocampal neurons [2], but little is known regarding the molecular mechanisms of this modulation. We show that Cav1.2 and NOP1 receptor form a complex and co-immunoprecipitate from transfected tsA201 cells and from hippocampal brain tissue. Calcium imaging of cultured rat hippocampal neurons treated with nociceptin (1uM) and depolarized with 40mM KCl revealed a significant decrease in calcium influx. Treatment with the LTCC blocker, Nifedipine showed that calcium influx is partially mediated by Cav1.2. Subsequent imaging of cultured rat hippocampal neurons treated with nociceptin (100nM) and depolarized with 40mM KCl revealed a significant decrease in CREB phosphorylation in the nucleus, an important step for neuronal plasticity. Treatments with Nifedipine and NMDA receptor antagonists (MK-801 and APV) indicate that the activation of nuclear p-CREB results in part from the activation of Cav1.2, and is NMDA receptor-independent. Our data provide novel insights into the mechanisms by which the endogenous neuropeptide nociceptin affects hippocampal neuron function. Ultimately, this could identify new strategies for the alleviation of memory disorders.
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How this classification was reachedexpand
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 | 0.001 | 0.002 |
| 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 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".