Neuron
Volume 68, Issue 5, 9 December 2010, Pages 843-856
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Neurotechnique
Superresolution Imaging of Chemical Synapses in the Brain

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Summary

Determination of the molecular architecture of synapses requires nanoscopic image resolution and specific molecular recognition, a task that has so far defied many conventional imaging approaches. Here, we present a superresolution fluorescence imaging method to visualize the molecular architecture of synapses in the brain. Using multicolor, three-dimensional stochastic optical reconstruction microscopy, the distributions of synaptic proteins can be measured with nanometer precision. Furthermore, the wide-field, volumetric imaging method enables high-throughput, quantitative analysis of a large number of synapses from different brain regions. To demonstrate the capabilities of this approach, we have determined the organization of ten protein components of the presynaptic active zone and the postsynaptic density. Variations in synapse morphology, neurotransmitter receptor composition, and receptor distribution were observed both among synapses and across different brain regions. Combination with optogenetics further allowed molecular events associated with synaptic plasticity to be resolved at the single-synapse level.

Highlights

► Superresolution fluorescence imaging of brain tissue ► High-throughput ultrastructural imaging of synapses ► High-precision position and orientation analyses of synaptic proteins ► Quantitative analyses of composition and plasticity of individual synapses

Cited by (0)

4

These authors contributed equally to this work

5

Present address: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA

6

Present address: Department of Pharmaceutical Chemistry, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA