Fig. 9

AMPAR subunits diffuse as monomers and dimers between the dendritic shaft and the synaptic region. Schematic figure showing that the AMPAR subunits GluA1 and GluA2 predominantly exist as monomers, and occasionally form transient dimers (and less frequently transient trimers and tetramers) in their reserve pools in the dendritic-shaft PM, where the subunit concentrations are low. Monomers and dimers diffuse quite freely in the dendritic-shaft PM, and enter the spines. In the synaptic regions in the spines, where the AMPAR subunit concentrations are high due to their binding to (plus their transient associations with) scaffolding protein complexes, including PSD95, GRIP, and SAP97⁵⁴, by way of TARP2, tetramers would be the predominant species, which work as l-glutamate-evoked channels. However, the tetramer lifetimes are quite short (a lifetime of 208 ms for the heterotetramers of GluA1 and GluA2, which could be prolonged due to their binding to scaffolding protein complexes). Namely, even in the synaptic regions, tetramers become dissociated readily, whereas monomers turn into tetramers extremely quickly. In this manner, AMPARs with different compositions could be formed readily. Meanwhile, the AMPAR subunit monomers can exit from the synaptic regions quickly, further enhancing the AMPAR composition changes when they are required. This would be useful after LTP induction. As such, the associations and dissociations of AMPAR subunits would play critical roles in regulating the AMPAR functions in the synaptic membrane