A Role for Calcium-Permeable AMPA Receptors in Synaptic Plasticity and Learning
Open Access
- 29 September 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 5 (9), e12818
- https://doi.org/10.1371/journal.pone.0012818
Abstract
A central concept in the field of learning and memory is that NMDARs are essential for synaptic plasticity and memory formation. Surprisingly then, multiple studies have found that behavioral experience can reduce or eliminate the contribution of these receptors to learning. The cellular mechanisms that mediate learning in the absence of NMDAR activation are currently unknown. To address this issue, we examined the contribution of Ca2+-permeable AMPARs to learning and plasticity in the hippocampus. Mutant mice were engineered with a conditional genetic deletion of GluR2 in the CA1 region of the hippocampus (GluR2-cKO mice). Electrophysiology experiments in these animals revealed a novel form of long-term potentiation (LTP) that was independent of NMDARs and mediated by GluR2-lacking Ca2+-permeable AMPARs. Behavioral analyses found that GluR2-cKO mice were impaired on multiple hippocampus-dependent learning tasks that required NMDAR activation. This suggests that AMPAR-mediated LTP interferes with NMDAR-dependent plasticity. In contrast, NMDAR-independent learning was normal in knockout mice and required the activation of Ca2+-permeable AMPARs. These results suggest that GluR2-lacking AMPARs play a functional and previously unidentified role in learning; they appear to mediate changes in synaptic strength that occur after plasticity has been established by NMDARs.Keywords
This publication has 80 references indexed in Scilit:
- Increased Insertion of Glutamate Receptor 2-Lacking α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid (AMPA) Receptors at Hippocampal Synapses upon Repeated Morphine AdministrationMolecular Pharmacology, 2010
- Activin A Is Essential for Neurogenesis Following NeurodegenerationThe International Journal of Cell Cloning, 2009
- Ca2+ Permeable AMPA Receptor Induced Long-Term Potentiation Requires PI3/MAP Kinases but Not Ca/CaM-Dependent Kinase IIPLOS ONE, 2009
- Recruitment of Calcium-Permeable AMPA Receptors during Synaptic Potentiation Is Regulated by CaM-Kinase IJournal of Neuroscience, 2008
- Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine cravingNature, 2008
- Roles of distinct glutamate receptors in induction of anti‐Hebbian long‐term potentiationThe Journal of Physiology, 2008
- Synaptic AMPA receptor subunit trafficking is independent of the C terminus in the GluR2-lacking mouseProceedings of the National Academy of Sciences of the United States of America, 2008
- Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTPThe EMBO Journal, 2007
- Anti-Hebbian Long-Term Potentiation in the Hippocampal Feedback Inhibitory CircuitScience, 2007
- NMDA Receptor Modulation of Incidental Learning in Pavlovian Context Conditioning.Behavioral Neuroscience, 2004