title: Nanoscale scaffolding domains within the postsynaptic density concentrate synaptic AMPA receptors.
abstract: Scaffolding molecules at the postsynaptic membrane form the foundation of excitatory synaptic transmission by establishing the architecture of the postsynaptic density (PSD), but the small size of the synapse has precluded measurement of PSD organization in live cells. We measured the internal structure of the PSD in live neurons at approximately 25 nm resolution using photoactivated localization microscopy (PALM). We found that four major PSD scaffold proteins were each organized in distinctive ∼80 nm ensembles able to undergo striking changes over time. Bidirectional PALM and single-molecule immunolabeling showed that dense nanodomains of PSD-95 were preferentially enriched in AMPA receptors more than NMDA receptors. Chronic suppression of activity triggered changes in PSD interior architecture that may help amplify synaptic plasticity. The observed clustered architecture of the PSD controlled the amplitude and variance of simulated postsynaptic currents, suggesting several ways in which PSD interior organization may regulate the strength and plasticity of neurotransmission.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Harold D
authors.initials: HD
authors.lastname: MacGillavry
authors.forename: Yu
authors.initials: Y
authors.lastname: Song
authors.forename: Sridhar
authors.initials: S
authors.lastname: Raghavachari
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Blanpied
mesh_terms: D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D008856:Microscopy, Fluorescence / Q000379:methods; D049329:Nanostructures; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D057907:Post-Synaptic Density / Q000502:physiology*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018091:Receptors, AMPA