Endogenous Cholinergic Input to the Pontine REM Sleep Generator Is Not Required for REM Sleep to Occur
Bibliographic record
Abstract
Initial theories of rapid eye movement (REM) sleep generation posited that induction of the state required activation of the pontine subceruleus (SubC) by cholinergic inputs. Although the capacity of cholinergic neurotransmission to contribute to REM sleep generation has been established, the role of cholinergic inputs in the generation of REM sleep is ultimately undetermined as the critical test of this hypothesis (local blockade of SubC acetylcholine receptors) has not been rigorously performed. We used bilateral microdialysis in freely behaving rats (n = 32), instrumented for electroencephalographic and electromyographic recording, to locally manipulate neurotransmission in the SubC with select drugs. As predicted, combined microperfusion of D-AP5 (glutamate receptor antagonist) and muscimol (GABAA receptor agonist) in the SubC virtually eliminated REM sleep. However, REM sleep was not reduced by scopolamine microperfusion in this same region, at a concentration capable of blocking the effects of cholinergic receptor stimulation. This result suggests that transmission of REM sleep drive to the SubC is acetylcholine-independent. Although SubC cholinergic inputs are not majorly involved in REM sleep generation, they may perform a minor function in the reinforcement of transitions into REM sleep, as evidenced by increases in non-REM-to-REM sleep transition duration and failure rate during cholinergic receptor blockade. Cholinergic receptor antagonism also attenuated the normal increase in hippocampal θ oscillations that characterize REM sleep. Using computational modeling, we show that our in vivo results are consistent with a mutually excitatory interaction between the SubC and cholinergic neurons where, importantly, cholinergic neuron activation is gated by SubC activity.
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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 | 0.002 | 0.011 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.003 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".