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Related Experiment Video

Updated: Feb 20, 2026

Long-term Potentiation of Perforant Pathway-dentate Gyrus Synapse in Freely Behaving Mice
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Grin2b 3'UTR is necessary for synaptic plasticity and spatial learning.

Alex C Harvey1,2,3, Ulrik Bølcho2,3,4, Bevan S Main5

  • 1Department of Molecular Biology and Genetics, Aarhus University, Aarhus 8000, Denmark.

Proceedings of the National Academy of Sciences of the United States of America
|February 18, 2026
PubMed
Summary
This summary is machine-generated.

The 3' untranslated region (3'UTR) of the GRIN2B gene is essential for synaptic plasticity and cognitive function. Deleting this region in mice reduced GluN2B protein, impaired learning, and blocked long-term potentiation.

Keywords:
NMDARNAlearningsynapse

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Spatially precise protein synthesis is crucial for synaptic plasticity and cognitive functions.
  • The GRIN2B transcript encodes the GluN2B subunit of NMDA receptors and possesses a long 3'UTR of unknown function.

Purpose of the Study:

  • To investigate the role of the 3'UTR of the GRIN2B transcript in synaptic function and cognition.
  • To determine the impact of GRIN2B 3'UTR deletion on GluN2B protein levels, localization, and receptor function.

Main Methods:

  • Generation of a mouse line with a deleted 3'UTR of the GRIN2B gene (∆3'UTR mice).
  • Quantification of GRIN2B mRNA and GluN2B protein levels in wildtype (WT) and ∆3'UTR mice.
  • Assessment of GRIN2B mRNA enrichment in synaptosomes and GluN2B phosphorylation.
  • Evaluation of long-term potentiation (LTP) and hippocampal-dependent spatial learning in both mouse lines.

Main Results:

  • Deletion of the GRIN2B 3'UTR in ∆3'UTR mice led to a 50% reduction in GluN2B protein, despite unchanged mRNA levels.
  • Impaired enrichment of GRIN2B mRNA in synaptosomes and reduced GluN2B phosphorylation were observed in ∆3'UTR mice.
  • ∆3'UTR mice exhibited deficits in LTP and hippocampal-dependent spatial learning.

Conclusions:

  • The 3'UTR of GRIN2B is critical for regulating GluN2B protein levels and synaptic localization.
  • The GRIN2B 3'UTR plays a vital role in synaptic plasticity and spatial learning.
  • These findings highlight the importance of 3'UTR regulation in neuronal function and cognitive processes.