Atypical NMDA Receptors Limit Synaptic Plasticity in the Adult Ventral Hippocampus
Bibliographic record
Abstract
Abstract N-methyl-D-aspartate receptors (NMDARs) assemble as functionally diverse heterotetramers. Incorporation of the GluN3A subunit into NMDARs alters conventional NMDAR properties by reducing both magnesium sensitivity and calcium permeability. GluN1 together with GluN3A can also form functional receptors that lack a glutamate binding site and instead serve as excitatory glycine receptors (eGlyRs). GluN3A expression is high in early development but naturally declines to low levels in most brain regions by adulthood. Interestingly, GluN3A expression remains elevated in the CA1 of the adult ventral hippocampus (VH), but not in the dorsal hippocampus (DH). The DH and VH are now well-understood to play very different functional roles, with the DH being primarily involved in cognitive functions and the VH in emotional processing. Why GluN3A persists in the adult VH, and the impact its presence has on glutamatergic neurotransmission in the VH is currently unknown. Here, we show that GluN3A remains elevated both at synaptic and extrasynaptic locations in the adult VH, assembling as GluN1/GluN2/GluN3A NMDARs with reduced magnesium sensitivity, as well as GluN1/GluN3A eGlyRs. By comparing various synaptic properties in the DH and VH of wild-type (WT) and GluN3A knockout (KO) mice, we demonstrate that GluN3A persistence in the VH attenuates glutamate release, limits postsynaptic calcium influx through NMDARs, and reduces the magnitude of NMDAR-dependent long-term potentiation. In comparison, GluN3A KO had relatively little effect on these same properties in the DH. In all, our data demonstrate that GluN3A persistence in the VH represents a key modulator of VH excitability and therefore may play a central role in emotional processing.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 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 | 0.001 |
| 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".