Glutamate receptor subunit GluA1 is necessary for long-term potentiation and synapse unsilencing, but not long-term depression in mouse hippocampus

Brain Res. 2012 Jan 30:1435:8-14. doi: 10.1016/j.brainres.2011.11.029. Epub 2011 Nov 19.

Abstract

Receptor subunit composition is believed to play a major role in the synaptic trafficking of AMPA receptors (AMPARs), and thus in activity-dependent synaptic plasticity. To isolate a physiological role of GluA1-containing AMPARs in area CA3 of the hippocampus, pair recordings were performed in organotypic hippocampal slices taken from genetically modified mice lacking the GluA1 subunit. We report here that long-term potentiation (LTP) is impaired not only at active but also at silent synapses when the GluA1 subunit is absent. The GluA1 knockout mice also exhibited reduced AMPAR-mediated evoked currents between pairs of CA3 pyramidal neurons under baseline conditions suggesting a significant role for GluA1-containing AMPARs in regulating basal synaptic transmission. In two independent measures, however, long-term depression (LTD) was unaffected in tissue from these mice. These data provide a further demonstration of the fundamental role that GluA1-containing AMPARs play in activity-dependent increases in synaptic strength but do not support a GluA1-dependent mechanism for reductions in synaptic strength.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Bicuculline / pharmacology
  • Biophysics
  • CA3 Region, Hippocampal / cytology*
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • GABA-A Receptor Antagonists / pharmacology
  • Long-Term Potentiation / physiology*
  • Long-Term Synaptic Depression / genetics
  • Long-Term Synaptic Depression / physiology*
  • Mice
  • Mice, Knockout
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Quinoxalines / pharmacology
  • Receptors, AMPA / deficiency
  • Receptors, AMPA / metabolism*
  • Sodium Channel Blockers / pharmacology
  • Synapses / physiology*
  • Tetrodotoxin / pharmacology

Substances

  • Excitatory Amino Acid Antagonists
  • GABA-A Receptor Antagonists
  • Quinoxalines
  • Receptors, AMPA
  • Sodium Channel Blockers
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Tetrodotoxin
  • glutamate receptor ionotropic, AMPA 1
  • Bicuculline