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PMID:21144999

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Citation

Dani, A, Huang, B, Bergan, J, Dulac, C and Zhuang, X (2010) Superresolution imaging of chemical synapses in the brain. Neuron 68:843-56

Abstract

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.

Links

PubMed PMC3057101 Online version:10.1016/j.neuron.2010.11.021

Keywords

Animals; Brain/metabolism; Brain/ultrastructure; Brain Chemistry/physiology; Image Processing, Computer-Assisted/instrumentation; Image Processing, Computer-Assisted/methods; Imaging, Three-Dimensional/instrumentation; Imaging, Three-Dimensional/methods; Immunohistochemistry/methods; Mice; Mice, Inbred C57BL; Microchemistry/methods; Microscopy, Fluorescence/instrumentation; Microscopy, Fluorescence/methods; Molecular Imaging/instrumentation; Molecular Imaging/methods; Nanotechnology; Nerve Tissue Proteins/metabolism; Nerve Tissue Proteins/ultrastructure; Neuronal Plasticity/physiology; Photomicrography/instrumentation; Photomicrography/methods; Presynaptic Terminals/metabolism; Presynaptic Terminals/ultrastructure; Stochastic Processes; Synapses/metabolism; Synapses/ultrastructure

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SHAN1

located_in

GO:0014069: postsynaptic density

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(UBERON:0005377)

Seeded From UniProt

complete

MOUSE:BSN

located_in

GO:0098831: presynaptic active zone cytoplasmic component

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(UBERON:0005377)|part_of:(UBERON:0004167)|part_of:(UBERON:0007631)

Seeded From UniProt

complete

MOUSE:GRIA1

located_in

GO:0098794: postsynapse

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(UBERON:0005377)

Seeded From UniProt

complete

MOUSE:NMDE2

located_in

GO:0098794: postsynapse

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(UBERON:0005377)

Seeded From UniProt

complete

MOUSE:DLG4

located_in

GO:0014069: postsynaptic density

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(UBERON:0005377)

Seeded From UniProt

complete

MOUSE:RIMS1

located_in

GO:0098831: presynaptic active zone cytoplasmic component

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(UBERON:0005377)

Seeded From UniProt

complete

MOUSE:PCLO

located_in

GO:0098831: presynaptic active zone cytoplasmic component

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(UBERON:0005377)

Seeded From UniProt

complete

MOUSE:GABR1

located_in

GO:0098793: presynapse

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(UBERON:0005377)

Seeded From UniProt

complete

MOUSE:HOME1

located_in

GO:0014069: postsynaptic density

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(UBERON:0005377)|part_of:(UBERON:0004167)|part_of:(UBERON:0007631)

Seeded From UniProt

complete

MOUSE:BSN

part_of

GO:0098831: presynaptic active zone cytoplasmic component

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(UBERON:0005377)|part_of:(UBERON:0004167)|part_of:(UBERON:0007631)

Seeded From UniProt

complete

MOUSE:NMDE2

part_of

GO:0098794: postsynapse

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(UBERON:0005377)

Seeded From UniProt

complete

MOUSE:HOME1

part_of

GO:0014069: postsynaptic density

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(UBERON:0005377)|part_of:(UBERON:0004167)|part_of:(UBERON:0007631)

Seeded From UniProt

complete

MOUSE:DLG4

part_of

GO:0014069: postsynaptic density

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(UBERON:0005377)

Seeded From UniProt

complete

MOUSE:GRIA1

part_of

GO:0098794: postsynapse

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(UBERON:0005377)

Seeded From UniProt

complete

MOUSE:SHAN1

part_of

GO:0014069: postsynaptic density

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(UBERON:0005377)

Seeded From UniProt

complete

MOUSE:GABR1

part_of

GO:0098793: presynapse

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(UBERON:0005377)

Seeded From UniProt

complete

Notes

See also

References

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