Thalamic δ-Subunit Containing GABA <sub>A</sub> Receptors Promote Electrocortical Signatures of Deep Non-REM Sleep But Do Not Mediate the Effects of Etomidate at the Thalamus <i>In Vivo</i>
Bibliographic record
Abstract
Extrasynaptic δ-subunits containing GABAA receptors (δGABAARs) are sensitive targets for several commonly used hypnotic agents and mediate tonic neuronal inhibition. δGABAARs are highly expressed within the thalamus and their activation promotes a switch from tonic to burst firing in vitro. Here we test two hypotheses in vivo. (1) Activation of thalamic δGABAARs will elicit electrocortical signatures consistent with widespread thalamocortical burst firing such as increased delta oscillations (1-4 Hz) and reciprocal changes in spindle-like oscillations (7-14 Hz). (2) These signatures will be recapitulated by the general anesthetic etomidate, if the electrocortical effects of etomidate at the thalamus are mediated by δGABAARs. Microperfusion of the δGABAAR-preferring agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP; 10 and 50 μM) into the ventrobasal complex produced significant effects on electrocortical activity in wild-type mice, but not in mice lacking δGABAARs (Gabrd(-/-)), i.e., the effects with THIP were dependent on δGABAARs. THIP (1) increased 1-4 Hz power in wakefulness and nonrapid-eye movement (NREM) sleep; (2) reduced spindle-like oscillations in NREM sleep; and (3) increased the speed of stable transitions into NREM sleep, indicating effects on state-space dynamics. In contrast, microperfusion of etomidate (10 and 30 μM) into the ventrobasal complex produced effects on electrocortical activity that were independent of δGABAARs, i.e., effects occurred in wild-type and Gabrd(-/-) mice. Etomidate (1) decreased 1-4 Hz power, increased 8-12 Hz, and/or 12-30 Hz power in all sleep-wake states; (2) increased spindle-like oscillations; and (3) increased REM sleep expression. These results indicate that thalamic δGABAARs promote electrocortical signatures of deep NREM sleep, but do not mediate the effects of etomidate at the thalamus in vivo.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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".