Subunit composition of synaptic AMPA receptors revealed by a single-cell genetic approach.
The precise subunit composition of synaptic ionotropic receptors in the brain is poorly understood. This information is of particular importance with regard to AMPA-type glutamate receptors, the multimeric complexes assembled from GluA1-A4 subunits, as the trafficking of these receptors into and out of synapses is proposed to depend upon the subunit composition of the receptor. We report a molecular quantification of synaptic AMPA receptors (AMPARs) by employing a single-cell genetic approach coupled with electrophysiology in hippocampal CA1 pyramidal neurons. In contrast to prevailing views, we find that GluA1A2 heteromers are the dominant AMPARs at CA1 cell synapses (approximately 80%). In cells lacking GluA1, -A2, and -A3, synapses are devoid of AMPARs, yet synaptic NMDA receptors (NMDARs) and dendritic morphology remain unchanged. These data demonstrate a functional dissociation of AMPARs from trafficking of NMDARs and neuronal morphogenesis. This study provides a functional quantification of the subunit composition of AMPARs in the CNS and suggests novel roles for AMPAR subunits in receptor trafficking.
Lu
Wei
W
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
Shi
Yun
Y
Jackson
Alexander C
AC
Bjorgan
Kirsten
K
During
Matthew J
MJ
Sprengel
Rolf
R
Seeburg
Peter H
PH
Nicoll
Roger A
RA
D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D018091:Receptors, AMPA / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D049452:Green Fluorescent Proteins; D021122:Protein Subunits; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter; C104723:glutamate receptor ionotropic, AMPA 3; C104722:glutamate receptor ionotropic, AMPA 2