Control of Long-Term Synaptic Potentiation and Learning by Alternative Splicing of the NMDA Receptor Subunit GluN1.
Alternative Splicing
Animals
Autism Spectrum Disorder
/ genetics
Cell Death
/ genetics
Cell Differentiation
Excitatory Postsynaptic Potentials
/ physiology
Exons
Hippocampus
/ metabolism
Humans
Induced Pluripotent Stem Cells
/ metabolism
Long-Term Potentiation
/ genetics
Mice
Mice, Knockout
Nerve Tissue Proteins
/ deficiency
Neurons
/ metabolism
Primary Cell Culture
Protein Subunits
/ deficiency
Receptors, N-Methyl-D-Aspartate
/ deficiency
Spatial Memory
/ physiology
Synapses
/ metabolism
Synaptic Transmission
GluN1
N1 cassette
NMDA Receptor
autism
long-term potentiation
splicing
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
24 12 2019
24 12 2019
Historique:
received:
16
05
2019
revised:
05
10
2019
accepted:
21
11
2019
entrez:
26
12
2019
pubmed:
26
12
2019
medline:
25
9
2020
Statut:
ppublish
Résumé
NMDA receptors (NMDARs) are critical for physiological synaptic plasticity, learning, and memory and for pathological plasticity and neuronal death. The GluN1 subunit is encoded by a single gene, GRIN1, with 8 splice variants, but whether the diversity generated by this splicing has physiological consequences remains enigmatic. Here, we generate mice lacking from the GluN1 exon 5-encoded N1 cassette (GluN1a mice) or compulsorily expressing this exon (GluN1b mice). Despite no differences in basal synaptic transmission, long-term potentiation in the hippocampus is significantly enhanced in GluN1a mice compared with that in GluN1b mice. Furthermore, GluN1a mice learn more quickly and have significantly better spatial memory performance than do GluN1b mice. In addition, in human iPSC-derived neurons in autism spectrum disorder NMDARs show characteristics of N1-lacking GluN1. Our findings indicate that alternative splicing of GluN1 is a mechanism for controlling physiological long-lasting synaptic potentiation, learning, and memory.
Identifiants
pubmed: 31875540
pii: S2211-1247(19)31585-2
doi: 10.1016/j.celrep.2019.11.087
pii:
doi:
Substances chimiques
GRIN1 protein, human
0
Gprin1 protein, mouse
0
Nerve Tissue Proteins
0
Protein Subunits
0
Receptors, N-Methyl-D-Aspartate
0
N-methyl D-aspartate receptor subtype 2A
VH92ICR8HX
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4285-4294.e5Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.