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Super-resolution microscopy: nano-scale spotlight for discovery of new principle in brain operation

開催日 2014/9/13
時間 9:00 - 11:00
会場 Room C(502)
Chairperson(s) 林 康紀 / Yasunori Hayashi (独立行政法人理化学研究所 脳科学総合研究センター / RIKEN Brain Science Institute, Japan)
坂内 博子 / Hiroko Bannai (名古屋大学大学院理学研究科生命理学専攻 / Department of Biological Science, Graduate School of Science, Nagoya University, Japan)

Activity-dependent dynamic substructure of single postsynaptic densities and the control of synapse function

  • S3-C-1-4
  • Thomas Blanpied:1 
  • 1:University of Maryland School of Medicine, Baltimore, USA 

Postsynaptic structure has the potential to control synaptic transmission in a number of as yet untested ways. For instance, although the size of the postsynaptic density (PSD) correlates with the total number of presynaptic vesicles, the number of synaptic AMPA receptors correlates poorly with the presynaptic release probability following an action potential. In addition, numerical modeling suggests that fusion of single vesicles activates AMPARs with high probability only in a small (~100 nm) region near the site of fusion. Since receptor distribution within the PSD is likely established by the organization of proteins in the PSD, we used single-molecule PALM imaging to assess the distribution of mEos2-tagged scaffolds in single PSDs of living hippocampal neurons. We found that PSD-95, GKAP, Shank, and Homer each were each organized in distinctive nano-domains ~80 nm in diameter. Within these scaffold-enhanced subdomains, the AMPAR subunit GluA2 and the NMDAR subunit GluN2B identified by STORM were enriched compared to their densities elsewhere in the PSD. Conversely, expressed GluA2-mEos3 was enriched in subsynaptic clusters that themselves colocalized with endogenous PSD-95. Notably, PSD structural features varied considerably across synapses, changed over time in a single synapse, and were modulated by NMDAR-stimulated and homeostatic plasticity. Actin, via Shank, drove acute changes in the PSD interior organization. To assess the functional impact of this intricate, plastic structure, we fed the measured map of receptors into existing models of geometrically realistic synapses, and found that the clustered distribution controlled the amplitude and variance of simulated postsynaptic currents. Thus, the alignment of release sites with postsynaptic clusters may strongly affect postsynaptic activation of either AMPARs or GluN2B receptors. Reading out super-resolved PSD structure concurrent with detailed, individualized function for many synapses in parallel will provide a powerful new approach to elucidate nanostructural control of synaptic plasticity.

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