Subunit composition of synaptic AMPA receptors revealed by a single-cell genetic approach
By Wei Dang Lu, Y. Shi, A. C. Jackson, Kirsten M. Bjorgan, M. During, R. Sprengel, P. Seeburg, R. Nicoll. Neuron, 2009
675 citations recorded by the source corpus.
Summary 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 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.
Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Neurology
View Paper: https://www.semanticscholar.org/paper/87cf85ea4b1e3febd2090d018c6d9f0c450583eb
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Citations in the corpus
- Regulation of AMPA Receptor Trafficking and Synaptic Plasticity (2012, background): “AMPARs are assembled as two identical heterodimers with GluA1/2 being the most predominant AMPAR subtype in hippocampal pyramidal neurons, followed by GluA2/3 heteromers [3 ].”
- Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future (2023, background): “α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is another glutamate receptor containing four subunits GluA1-4, which makes up to 80% of the excitatory synapses in the CA1 region of hippocampus.(81,82) Many studies have shown that AMPARs also take part in the modulation of syna”
- AMPARs and synaptic plasticity: the last 25 years. (2013, neutral): “The major forms of receptors in the hippocampus include GluA1/2 and GluA2/3 heteromers as well as GluA1 homomers (Lu et al., 2009; Wenthold et al., 1996).”
- Assembly of a β2‐adrenergic receptor—GluR1 signalling complex for localized cAMP signalling (2010, background): “Assembly of all proteins in- volved in the classic b2AR–cAMP cascade into a supramolecular signalling complex and thus allows highly localized and selective regulation of one of its major target proteins.”