Disparate Effects of Lithium and a GSK-3 Inhibitor on Neuronal Oscillatory Activity in Prefrontal Cortex and Hippocampus
Bibliographic record
Abstract
Glycogen synthase kinase-3 (GSK-3) plays a critical role in cognitive dysfunction associated with Alzheimer's disease (AD), yet the mechanism by which GSK-3 alters cognitive processes in other disorders, such as schizophrenia, remains unknown. In the present study, we demonstrated a role for GSK-3 in the direct regulation of neuronal oscillations in hippocampus (HIP) and prelimbic cortex (PL). A comparison of the GSK-3 inhibitors SB 216763 and lithium demonstrated disparate effects of the drugs on spatial memory and neural oscillatory activity in HIP and PL. SB 216763 administration improved spatial memory whereas lithium treatment had no effect. Analysis of neuronal local field potentials in anesthetized animals revealed that whereas both repeated SB 216763 (2.5 mg/kg) and lithium (100 mg/kg) induced a theta frequency spike in HIP at approximately 10 Hz, only SB 216763 treatment induced an overall increase in theta power (4-12 Hz) compared to vehicle. Acute administration of either drug suppressed slow (32-59 Hz) and fast (61-100 Hz) gamma power. In PL, both drugs induced an increase in theta power. Repeated SB 216763 increased HIP-PL coherence across all frequencies except delta, whereas lithium selectively suppressed delta coherence. These findings demonstrate that GSK-3 plays a direct role in the regulation of theta oscillations in regions critically involved in cognition, and highlight a potential mechanism by which GSK-3 may contribute to cognitive decline in disorders of cognitive dysfunction.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.003 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".