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Genetic analysis of neuronal ionotropic glutamate receptor subunits
Author(s) -
Granger Adam J.,
Gray John A.,
Lu Wei,
Nicoll Roger A.
Publication year - 2011
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2011.213033
Subject(s) - ampa receptor , ionotropic effect , ionotropic glutamate receptor , nmda receptor , long term depression , neuroscience , neurotransmission , ion channel linked receptors , synaptic plasticity , biology , silent synapse , glutamate receptor , kainate receptor , microbiology and biotechnology , chemistry , receptor , biochemistry
In the brain, fast, excitatory synaptic transmission occurs primarily through AMPA‐ and NMDA‐type ionotropic glutamate receptors. These receptors are composed of subunit proteins that determine their biophysical properties and trafficking behaviour. Therefore, determining the function of these subunits and receptor subunit composition is essential for understanding the physiological properties of synaptic transmission. Here, we discuss and evaluate various genetic approaches that have been used to study AMPA and NMDA receptor subunits. These approaches have demonstrated that the GluA1 AMPA receptor subunit is required for activity‐dependent trafficking and contributes to basal synaptic transmission, while the GluA2 subunit regulates Ca 2+ permeability, homeostasis and trafficking to the synapse under basal conditions. In contrast, the GluN2A and GluN2B NMDA receptor subunits regulate synaptic AMPA receptor content, both during synaptic development and plasticity. Ongoing research in this field is focusing on the molecular interactions and mechanisms that control these functions. To accomplish this, molecular replacement techniques are being used, where native subunits are replaced with receptors containing targeted mutations. In this review, we discuss a single‐cell molecular replacement approach which should arguably advance our physiological understanding of ionotropic glutamate receptor subunits, but is generally applicable to study of any neuronal protein.