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PMID: 21144999 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Superresolution imaging of chemical synapses in the brain.

Neuron ·Vol. 68 ·No. 5 ·2010-12-09 ·Pages 843-56

Dani A, Huang B, Bergan J, Dulac C, Zhuang X

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.

MeSH Terms
Animals Brain/metabolism,ultrastructure Brain Chemistry/physiology Image Processing, Computer-Assisted/instrumentation,methods Imaging, Three-Dimensional/instrumentation,methods Immunohistochemistry/methods Mice Mice, Inbred C57BL Microchemistry/methods Microscopy, Fluorescence/instrumentation,methods Molecular Imaging/instrumentation,methods Nanotechnology Nerve Tissue Proteins/metabolism,ultrastructure Neuronal Plasticity/physiology Photomicrography/instrumentation,methods Presynaptic Terminals/metabolism,ultrastructure Stochastic Processes Synapses/metabolism,ultrastructure
Chemicals
Nerve Tissue Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Dani Adish
Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
Huang Bo
Bergan Joseph
Dulac Catherine
Zhuang Xiaowei
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
DOI
10.1016/j.neuron.2010.11.021
Published
2010-12-09
Pages
843-56
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC3057101
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NIDCD NIH HHS · F32 DC010089 · United States
NIDCD NIH HHS · R01 DC009019 · United States
Howard Hughes Medical Institute · 43667 · United States
External Links
PubMed source DOI: 10.1016/j.neuron.2010.11.021 PMC Full Text View journal details
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