Discharge and Role of Acetylcholine Pontomesencephalic Neurons in Cortical Activity and Sleep-Wake States Examined by Optogenetics and Juxtacellular Recording in Mice
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Bibliographic record
Abstract
Acetylcholine (ACh) neurons in the pontomesencephalic tegmentum (PMT) are thought to play an important role in promoting cortical activation with waking (W) and paradoxical sleep [PS; or rapid eye movement (REM)], but have yet to be proven to do so by selective stimulation and simultaneous recording of identified ACh neurons. Here, we employed optogenetics combined with juxtacellular recording and labeling of neurons in transgenic (TG) mice expressing ChR2 in choline acetyltransferase (ChAT)-synthesizing neurons. We established in vitro then in vivo in anesthetized (A) and unanesthetized (UA), head-fixed mice that photostimulation elicited a spike with short latency in neurons which could be identified by immunohistochemical staining as ACh neurons within the laterodorsal (LDT)/sublaterodorsal (SubLDT) and pedunculopontine tegmental (PPT) nuclei. Continuous light pulse stimulation during sleep evoked tonic spiking by ACh neurons that elicited a shift from irregular slow wave activity to rhythmic θ and enhanced γ activity on the cortex without behavioral arousal. With θ frequency rhythmic light pulse stimulation, ACh neurons discharged in bursts that occurred in synchrony with evoked cortical θ. During natural sleep-wake states, they were virtually silent during slow wave sleep (SWS), discharged in bursts during PS and discharged tonically during W. Yet, their bursting during PS was not rhythmic or synchronized with cortical θ but associated with phasic whisker movements. We conclude that ACh PMT neurons promote θ and γ cortical activity during W and PS by their tonic or phasic discharge through release of ACh onto local neurons within the PMT and/or more distant targets in the hypothalamus and thalamus.
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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 | 0.000 | 0.001 |
| 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 | 0.000 |
| 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 it