The Requirement of the C-Terminal Domain of GluA1 in Different Forms of Long-Term Potentiation in the Hippocampus Is Age-Dependent
Bibliographic record
Abstract
Long-term potentiation (LTP) at glutamatergic synapses is an extensively studied form of long-lasting synaptic plasticity widely regarded as the cellular basis for learning and memory. At the CA1 synapse, there are multiple forms of LTP with distinct properties. Although AMPA gluta-mate receptors (AMPARs) are a key target of LTP expression, whether they are required in all forms of LTP remains unclear. To address this question, we have used our recently developed mouse line, GluA1C2KI, where the c-terminal domain (CTD) of the endogenous GluA1 is replaced by that of GluA2. Unlike traditional GluA1 global or conditional KO mice, GluA1C2KI mice have no changes in basal AMPAR properties or synaptic transmission allowing a better assessment of GluA1 in synaptic plasticity. We previously showed that these mice are impaired in LTP induced by high frequency stimulation (HFS-LTP), but whether other forms of LTP are also affected in these mice is unknown. In this study, we compared various forms of LTP at CA1 synapses be-tween GluA1C2KI and wild-type littermates by using several induction protocols. We show that HFS-LTP is impaired in both juvenile and adult GluA1C2KI mice. The LTP induced by theta-burst stimulation (TBS-LTP) is also abolished in juvenile GluA1C2KI mice. Interestingly, TBS-LTP can still be induced in adult GluA1C2KI mice, but its mechanisms are altered becoming more sensitive to protein synthesis and the extracellular signal-regulated kinase (ERK) inhibitors compared to wild type control. The GluA1C2KI mice are also differentially altered in several forms of LTP in-duced under whole-cell recording paradigms. These results indicate that the CTD of GluA1 is dif-ferentially involved in different forms of LTP at CA1 synapse highlighting the complexity and adaptative potential of LTP expression mechanisms in the hippocampus.
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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) | 0.001 | 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 | 0.001 |
| 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".