1-B-38 - Atypical NMDA receptors limit synaptic plasticity in the adult ventral hippocampus
Bibliographic record
Abstract
Authors: Emily Hurley¹, Bandhan Mukerjee¹, Jocelyn Adundo¹, Firoozeh Nafar¹, Matthew Parsons¹ ¹Memorial University of Newfoundland Abstract: The dorsal and ventral hippocampus (DH and VH) are dramatically different structures. The DH is involved in cognition and undergoes robust synaptic plasticity while the VH functions in emotional processing and naturally exhibits poor plasticity. N-methyl-D-aspartate receptors (NMDARs) assemble as functionally diverse heterotetramers with essential roles in synaptic plasticity. Incorporation of the GluN3A subunit into NMDARs alters conventional NMDAR properties, delays synapse maturity, and opposes synaptic plasticity. Consistent with recent reports, we show that GluN3A remains elevated, mainly in extrasynaptic locations, in the adult VH but not the DH. Despite GluN3A persistence, VH spines matched the maturity level observed for the DH. As presynaptic and postsynaptic GluN3A-NMDARs can facilitate glutamate release and limit Ca2+ permeability, we performed real-time glutamate and calcium imaging to further understand the consequences of GluN3A persistence in the adult VH. Compared to the DH, the VH accumulated more glutamate during afferent stimulation yet exhibited less NMDAR-mediated Ca2+ influx. We then hypothesized that prolonged GluN3A expression limits synaptic plasticity in the VH. Indeed, in wildtype mice, long-term potentiation (LTP) was significantly lower in the VH compared to the DH. In contrast, GluN3A knockout (KO) mice exhibited strong VH LTP that now exceeded the magnitude of LTP in the DH. In sum, our data show that GluN3A persistence limits VH plasticity in adulthood, perhaps serving a protective role to prevent overexcitation of anxiety and fear circuitry.
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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 | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.010 | 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".