Src inhibition reduces NR2B surface expression and synaptic plasticity in the amygdala
Why this work is in the frame
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Bibliographic record
Abstract
The Src protein tyrosine kinase plays a central role in the regulation of N-methyl-d-aspartate receptor (NMDAR) activity by regulating NMDAR subunit 2B (NR2B) surface expression. In the amygdala, NMDA-dependent synaptic plasticity resulting from convergent somatosensory and auditory inputs contributes to emotional memory; however, the role of Src tyrosine kinase has not been investigated. We have synthesized a Src-derived peptide, Tat-Src (40-58), that crosses the blood-brain barrier following injection and accumulates intracellularly. Tat-Src (40-58) blocks the interaction of Src with NMDA receptors. Following injection, mice demonstrate impaired amygdala-dependent cued fear conditioning, as well as impairments in an amygdala-dependent nonassociative social recognition task. The Src inhibitor decreased NR2B phosphorylation in amygdala tissue and reduced NR2B surface expression in cultured amygdala neurons with a concomitant reduction in NMDA multimer-containing dendritic puncta. In addition, preincubation of this inhibitory peptide blocked amygdalar long-term potentiation in the lateral to basolateral pathway in vitro. These results indicate that Src is a key regulator of NMDAR trafficking in the amygdala. Furthermore, Src-dependent phosphorylation of NR2B supports amygdala plasticity and amygdalar-dependent learning.
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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 | 0.001 | 0.002 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| 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