A screen of immune signaling molecules regulated by neuronal activity identifies interferon-gamma as a modulator of synaptic function and anxiety-like behavior
Bibliographic record
Abstract
A number of immune signaling molecules have been shown to act within the central nervous system to regulate neuronal function. To look for additional candidates, we conducted a screen of the expression of immune signaling molecules regulated by neuronal activity in the hippocampus. Hippocampal slice cultures were treated for 48 h with TTX (to block neuronal activity) or gabazine (to block GABA-A receptors and thus elevate neuronal activity). These treatments are known to trigger homeostatic synaptic plasticity, and regulate the expression of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF). The screen revealed a number of immune signaling molecules were upregulated by TTX, and a smaller subset upregulated by gabazine. We validated some of the more prominent responders, including Interferon gamma (IFNγ). We then tested the effects of IFNγ on synaptic function. IFNγ could acutely alter both glutamatergic and GABAergic synaptic function, and mice with deficient IFNγ signaling have altered anxiety-like behaviour, although only in males. These data support the idea that many signaling molecules initially characterized in the immune system have important endogenous regulatory roles within the CNS under non-pathological conditions.
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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 | 0.000 |
| 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) | 0.000 | 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".