Pentobarbital Depressant Effects Are Independent of GABA Receptors in Auditory Thalamic Neurons
Bibliographic record
Abstract
Pentobarbital, a general anesthetic, has received extensive study for its ability to potentiate inhibition at GABA(A) subtype of receptors for GABA. Using whole cell current-clamp techniques and bath applications, we determined the effects of pentobarbital and GABA receptor antagonists on the membrane properties and tonic or burst firing of medial geniculate neurons in thalamic slices. Pentobarbital (0.01-200 microM) induced depressant effects in 50 of 66 neurons (76%). Pentobarbital hyperpolarized neurons by a mean of 3 mV and decreased the number of action potentials in tonic firing, evoked by current pulse injection from near the resting potential. Pentobarbital also decreased burst firing or low threshold Ca(2+)-spikes, evoked by current pulse injection into neurons at potentials hyperpolarized from rest. The blockade of tonic and burst firing, as well as low threshold Ca(2+)-spikes, was surmountable by increasing the amplitude of input current. The GABA(A) receptor antagonists, bicuculline (100 microM) and picrotoxinin (50-100 microM), did not block the depressant effects of pentobarbital (10 microM). The GABA(B) receptor antagonist, saclofen (200 microM), and GABA(C) receptor antagonist, (1,2,3,6-tetrahydropyridine-4-yl)methylphosphinate (10-50 microM), did not significantly alter the depressant effects. Pentobarbital produced excitatory effects (0.1-50 microM) on 11 neurons (17%) but had no effects on 5 neurons (7%). The excitation consisted of approximately 3 mV depolarization, increased tonic and burst firing and the rate of rise and amplitude of low threshold Ca(2+) spikes. These effects were associated with a increase in input resistance. In contrast, the depressant effects of pentobarbital correlated to a decreased input resistance measured with hyperpolarizing current pulse injection (IC(50) = 7.8 microM). Pentobarbital reduced Na(+)-dependent rectification on depolarization and lowered the slope resistance over a wide voltage range. Tetrodotoxin eliminated both Na(+)-dependent rectification and the pentobarbital-induced decrease in membrane resistance at depolarized voltages in two-thirds of the neurons. The pentobarbital-induced decrease in membrane resistance at voltages hyperpolarized from rest was not evident during co-application with Cs(+), known to block the hyperpolarization-activated rectifiers. In summary, the pentobarbital acted at low concentrations to depress thalamocortical neurons. The depression resulted from decreased rectification on depolarization, which no longer boosted potentials over threshold, and an increased conductance that shunted spike generation. The depressant effects of pentobarbital did not involve known types of GABA receptor interactions.
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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 | 0.000 |
| 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".