The AMPA Receptor Subunit GluA1 is Required for CA1 Hippocampal Long-Term Potentiation but is not Essential for Synaptic Transmission

Neurochemical Research
Akira TerashimaJohn T R Isaac

Abstract

AMPA receptors mediate the majority of excitatory glutamatergic transmission in the mammalian brain and are heterotetramers composed of GluA1-4 subunits. Despite genetic studies, the roles of the subunits in synaptic transmission and plasticity remain controversial. To address this issue, we investigated the effects of cell-specific removal of GluA1 in hippocampal CA1 pyramidal neurons using virally-expressed GluA1 shRNA in organotypic slice culture. We show that this shRNA approach produces a rapid, efficient and selective loss of GluA1, and removed > 80% of surface GluA1 from synapses. This loss of GluA1 caused a modest reduction (up to 57%) in synaptic transmission and when applied in neurons from GluA3 knock-out mice, a similar small reduction in transmission occurred. Further, we found that loss of GluA1 caused a redistribution of GluA2 to synapses that may compensate functionally for the absence of GluA1. We found that LTP was absent in neurons lacking GluA1, induced either by pairing or by a theta-burst pairing protocol previously shown to induce LTP in GluA1 knock-out mice. Our findings demonstrate a critical role of GluA1 in CA1 LTP, but no absolute requirement for GluA1 in maintaining synaptic transmission. Further, o...Continue Reading

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Citations

Sep 10, 2020·Frontiers in Molecular Neuroscience·Manoj GovindarajuluRajesh H Amin
Dec 12, 2019·Frontiers in Endocrinology·Jenna BloemerVishnu Suppiramaniam
Jun 6, 2021·Neuropharmacology·Radu Gugustea, Zhengping Jia

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Methods Mentioned

BETA
density gradient centrifugation

Software Mentioned

Mini
Analysis

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