Agonist‐induced depression of cholinergic current in <i>Aplysia</i> bag cell neurons requires ionotropic acetylcholine receptor trafficking
Bibliographic record
Abstract
Abstract Cholinergic input initiates or regulates prolonged neuronal activity implicated in executive attention, learning and neuroendocrine control. In the hermaphroditic sea snail, Aplysia , ionotropic acetylcholine receptors on neuroendocrine bag cell neurons trigger an ∼30‐min afterdischarge that leads to egg‐laying hormone secretion and reproductive behaviour. The afterdischarge is followed by an ∼18‐h refractory period, where acetylcholine fails to cause further bursting. Here, we report on a similar long‐term depression of acetylcholine receptors in cultured bag cell neurons. Under whole‐cell voltage‐clamp, the current evoked by 2‐s pressure‐ejections of 1 mM acetylcholine exhibited persistent rundown, with partial recovery by 6 h after the first ejection and complete recovery at 24 h. Consecutive applications at 3‐, 10‐, 30‐, 60‐ or 90‐min intervals reliably yielded ∼two‐thirds of current remaining at the second ejection. Similar rundown was elicited using the cholinergic agonist tretramethylammonium, albeit at 10 mM. Rundown was independent of channel gating, as the acetylcholine receptor pore‐blocker hexamethonium failed to alter progression. Neither the protein kinase A blocker KT5720 nor the muscarinic receptor antagonist phenyltrimethylammonium affected rundown. However, the proteasome inhibitor lactacystin attenuated rundown, while disrupting the trans ‐Golgi network with brefeldin A or protein synthesis with anisomcyin prevented recovery 24 h later, consistent with receptor trafficking underlying both rundown and recovery. A decrease in receptor membrane density following acetylcholine was confirmed by confocal microscopy of neurons stained with the dye‐conjugated ionotropic antagonist ‐conotoxin ImI‐ATTO Fluor‐590. Hence, retrieval of receptors from the membrane mediates rundown and, analogous to the refractory period, may control the timing of reproduction. image Key points Hormone secretion from neuroendocrine cells typically requires a prolonged burst of action potentials; for example, bag cell neurons from the marine snail Aplysia trigger reproduction by the neurohaemal release of egg‐laying hormone during a lengthy afterdischarge. The bag cell neuron afterdischarge is initiated by cholinergic synaptic input onto ionotropic acetylcholine receptors, but following an afterdischarge, the neurons become unresponsive to acetylcholine for many hours. We now demonstrate that, after an initial exposure to acetylcholine, a proportion of these ionotropic receptors are internalized and made unavailable, without any influence from a metabotropic counterpart. This prolonged depression of cholinergic receptors also lasts many hours and likely serves to prevent disruption of ongoing bursting and/or the amount of hormone released. Therefore, changes in the number of ionotropic receptors at the membrane may influence the timing of neuroendocrine cell activity.
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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".