title: Mapping synapses by conjugate light-electron array tomography.
abstract: Synapses of the mammalian CNS are diverse in size, structure, molecular composition, and function. Synapses in their myriad variations are fundamental to neural circuit development, homeostasis, plasticity, and memory storage. Unfortunately, quantitative analysis and mapping of the brain's heterogeneous synapse populations has been limited by the lack of adequate single-synapse measurement methods. Electron microscopy (EM) is the definitive means to recognize and measure individual synaptic contacts, but EM has only limited abilities to measure the molecular composition of synapses. This report describes conjugate array tomography (AT), a volumetric imaging method that integrates immunofluorescence and EM imaging modalities in voxel-conjugate fashion. We illustrate the use of conjugate AT to advance the proteometric measurement of EM-validated single-synapse analysis in a study of mouse cortex.
authors: Department of Molecular and Cellular Physiology, Stanford School of Medicine, Stanford University, Stanford California 94305, Allen Institute for Brain Science, Seattle, Washington 98103 forrest.collman@gmail.com.
authors: Forrest
authors: http://orcid.org/0000-0002-0280-7022
authors: F
authors: Collman
authors: Department of Molecular and Cellular Physiology, Stanford School of Medicine, Stanford University, Stanford California 94305.
authors: JoAnn
authors: J
authors: Buchanan
authors: Department of Cell Biology and Physiology, University of North Carolina School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599.
authors: Kristen D
authors: KD
authors: Phend
authors: Department of Molecular and Cellular Physiology, Stanford School of Medicine, Stanford University, Stanford California 94305.
authors: Kristina D
authors: KD
authors: Micheva
authors: Department of Cell Biology and Physiology, University of North Carolina School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina 27599, and.
authors: Richard J
authors: RJ
authors: Weinberg
authors: Department of Molecular and Cellular Physiology, Stanford School of Medicine, Stanford University, Stanford California 94305, Allen Institute for Brain Science, Seattle, Washington 98103.
authors: Stephen J
authors: SJ
authors: Smith
mesh_terms: D000818:Animals; D001931:Brain Mapping; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D055032:Electron Microscope Tomography; D007091:Image Processing, Computer-Assisted; D008565:Membrane Proteins / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D008870:Microtubules / Q000648:ultrastructure; D019579:Neocortex / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*; D012044:Regression Analysis; D060388:Support Vector Machine; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure*; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050496:Vesicular Glutamate Transport Proteins; D005680:gamma-Aminobutyric Acid
keywords: correlative microscopy; electron microscopy; immunofluorescence; synapses; synaptic diversity