Publication Date:
2012-12-14
Description:
Long-term potentiation (LTP) of synaptic transmission is thought to be an important cellular mechanism underlying memory formation. A widely accepted model posits that LTP requires the cytoplasmic carboxyl tail (C-tail) of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GluA1. To find the minimum necessary requirement of the GluA1 C-tail for LTP in mouse CA1 hippocampal pyramidal neurons, we used a single-cell molecular replacement strategy to replace all endogenous AMPA receptors with transfected subunits. In contrast to the prevailing model, we found no requirement of the GluA1 C-tail for LTP. In fact, replacement with the GluA2 subunit showed normal LTP, as did an artificially expressed kainate receptor not normally found at these synapses. The only conditions under which LTP was impaired were those with markedly decreased AMPA receptor surface expression, indicating a requirement for a reserve pool of receptors. These results demonstrate the synapse's remarkable flexibility to potentiate with a variety of glutamate receptor subtypes, requiring a fundamental change in our thinking with regard to the core molecular events underlying synaptic plasticity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998843/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998843/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Granger, Adam J -- Shi, Yun -- Lu, Wei -- Cerpas, Manuel -- Nicoll, Roger A -- R01 MH070957/MH/NIMH NIH HHS/ -- England -- Nature. 2013 Jan 24;493(7433):495-500. doi: 10.1038/nature11775. Epub 2012 Dec 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neuroscience Graduate Program, University of California San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23235828" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Gene Deletion
;
Long-Term Potentiation/*physiology
;
Mice
;
Models, Neurological
;
Protein Structure, Tertiary
;
Protein Subunits/*metabolism
;
Protein Transport
;
Receptors, AMPA/chemistry/deficiency/genetics/metabolism
;
Receptors, Ionotropic Glutamate/*chemistry/*metabolism
;
Receptors, Kainic Acid/metabolism
;
Synapses/metabolism
;
Synaptic Transmission
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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