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Single-synapse analysis of a diverse synapse population: proteomic imaging methods and markers.

Neuron | Nov 18, 2010

A lack of methods for measuring the protein compositions of individual synapses in situ has so far hindered the exploration and exploitation of synapse molecular diversity. Here, we describe the use of array tomography, a new high-resolution proteomic imaging method, to determine the composition of glutamate and GABA synapses in somatosensory cortex of Line-H-YFP Thy-1 transgenic mice. We find that virtually all synapses are recognized by antibodies to the presynaptic phosphoprotein synapsin I, while antibodies to 16 other synaptic proteins discriminate among 4 subtypes of glutamatergic synapses and GABAergic synapses. Cell-specific YFP expression in the YFP-H mouse line allows synapses to be assigned to specific presynaptic and postsynaptic partners and reveals that a subpopulation of spines on layer 5 pyramidal cells receives both VGluT1-subtype glutamatergic and GABAergic synaptic inputs. These results establish a means for the high-throughput acquisition of proteomic data from individual cortical synapses in situ.

Pubmed ID: 21092855 RIS Download

Mesh terms: Animals | Biomarkers | Immunohistochemistry | Mice | Mice, Inbred C57BL | Mice, Transgenic | Microscopy, Fluorescence | Protein Array Analysis | Proteomics | Receptors, GABA | Synapses | Synapsins | Vesicular Glutamate Transport Protein 1 | Vesicular Glutamate Transport Protein 2

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Associated grants

  • Agency: NINDS NIH HHS, Id: R21 NS063210
  • Agency: NINDS NIH HHS, Id: R21 NS063210-01
  • Agency: NINDS NIH HHS, Id: R01 NS075252
  • Agency: Howard Hughes Medical Institute, Id: NS063210
  • Agency: NINDS NIH HHS, Id:

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