Social memory maintenance relies on social interaction-induced proteolytic products of neuroligin 1
Bibliographic record
Abstract
Proper social behaviors are essential for survival and success, and deficits in these behaviors are associated with many brain disorders. However, the mechanisms underlying the formation and maintenance of social memory remain poorly understood. In this study, we demonstrate that social interaction with unfamiliar mouse induces α- and γ-secretase-dependent proteolysis of Neuroligin 1 (NLG1) in the ventral hippocampus (vHPC). The intracellular hydrolysate fragment, NLG1-CTD, regulates synaptic plasticity, spine strengthening, and the maintenance of social memory through its PDZ binding domain (PBD) and the cofilin signaling pathway. Both γ-secretase inhibition and deletion of the secretase recognition site on NLG1 prevent cofilin phosphorylation and impair the maintenance of social memory by inhibiting the production of NLG1-CTD. Injection of the Tat-PBD peptide into the vHPC inhibits cofilin activity and rescues deficits in social memory maintenance in mouse models. Additionally, our findings indicate that deficits in maintaining memory for sequentially presented social objects within a short temporal interval may be associated with insufficient levels of NLG1-CTD. Supplementation of Tat-PBD into the vHPC promotes maturation of dendritic spines and restores the maintenance of memory for the second social object. We also discovered that NLG1-CTD/PBD may play a role in maintaining novel object recognition memory. In summary, this work uncovers a novel mechanism that links extracellular and intracellular signal transduction processes to synaptic remodeling during learning and memory maintenance, providing a systematic perspective that connects memory formation, maintenance, and synaptic structural and functional plasticity.
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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".