LTP requires a reserve pool of glutamate receptors independent of subunit type

Nature. 2013 Jan 24;493(7433):495-500. doi: 10.1038/nature11775. Epub 2012 Dec 12.


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 (α-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Gene Deletion
  • Long-Term Potentiation / physiology*
  • Mice
  • Models, Neurological
  • Protein Structure, Tertiary
  • Protein Subunits / metabolism*
  • Protein Transport
  • Receptors, AMPA / chemistry
  • Receptors, AMPA / deficiency
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism
  • Receptors, Ionotropic Glutamate / chemistry*
  • Receptors, Ionotropic Glutamate / metabolism*
  • Receptors, Kainic Acid / metabolism
  • Synapses / metabolism
  • Synaptic Transmission


  • Gluk1 kainate receptor
  • Protein Subunits
  • Receptors, AMPA
  • Receptors, Ionotropic Glutamate
  • Receptors, Kainic Acid
  • glutamate receptor ionotropic, AMPA 2
  • glutamate receptor ionotropic, AMPA 1