Subunit Composition of Synaptic AMPA Receptors Revealed by a Single-Cell Genetic Approach

• Published in: Neuron (Cambridge, Mass.) Mass.), 2009-04, Vol.62 (2), p.254-268
• Main Authors: Lu, Wei, Shi, Yun, Jackson, Alexander C., Bjorgan, Kirsten, During, Matthew J., Sprengel, Rolf, Seeburg, Peter H., Nicoll, Roger A.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Biophysics; Brain research; Electric Stimulation; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Glutamic Acid - pharmacology; Green Fluorescent Proteins - genetics; Hippocampus - cytology; In Vitro Techniques; Membrane Potentials - drug effects; Membrane Potentials - genetics; Membrane Potentials - physiology; Mice; Mice, Transgenic; Models, Neurological; MOLNEURO; Neurons; Neurons - drug effects; Neurons - physiology; Patch-Clamp Techniques; Polyamines; Protein Subunits - genetics; Protein Subunits - metabolism; Protein Transport - drug effects; Receptors, AMPA - deficiency; Receptors, AMPA - genetics; Receptors, AMPA - metabolism; Receptors, Neurotransmitter - genetics; Receptors, Neurotransmitter - metabolism; Rodents; SIGNALING
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2009.02.027

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 (∼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.