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Automated Analysis of a Diverse Synapse Population.doc

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Automated Analysis of a Diverse Synapse Population

AutomatedAnalysisofaDiverseSynapsePopulation BradBusse1,2*,StephenSmith3 1BiophysicsProgram,StanfordUniversity,Stanford,California,UnitedStatesofAmerica,2PrograminPhysicalBiology,EuniceKennedyShriverNationalInstituteofChild Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America, 3Department of Molecular and Cellular Physiology, StanfordUniversity,Stanford,California,UnitedStatesofAmerica Abstract Synapses of the mammalian central nervous system are highly diverse in function and molecular composition. Synapse diversity per se may be critical to brain function, since memory and homeostatic mechanisms are thought to be rooted primarilyinactivity-dependentplasticchangesinspecificsubsetsofindividualsynapses.Unfortunately,themeasurement ofsynapsediversityhasbeenrestrictedbythelimitationsofmethodscapableofmeasuringsynapsepropertiesatthelevel ofindividualsynapses.Arraytomographyisanewhigh-resolution,high-throughputproteomicimagingmethodthathas the potential to advance the measurement of unit-level synapse diversity across large and diverse synapse populations. Herewe presentan automatedfeature extractionand classification algorithmdesigned toquantify synapses fromhigh- dimensional array tomographic data too voluminous for manual analysis. We demonstrate the use of this method to quantify laminar distributions of synapses in mouse somatosensory cortex and validate the classification process by detectingthepresenceofknownbutuncommonproteomicprofiles.Suchclassificationandquantificationwillbehighly useful in identifying specific subpopulations of synapses exhibiting plasticity in response to perturbations from the environmentorthesensoryperiphery. Citation:BusseB,SmithS(2013)AutomatedAnalysisofaDiverseSynapsePopulation.PLoSComputBiol9(3):e1002976.doi:10.1371/journal.pcbi.1002976 Editor:MichaelHawrylycz,AllenInstituteforBrainScience,UnitedStatesofAmerica ReceivedJune1,2012;AcceptedJanuary21,2013;PublishedMarch28,2013 Thisisano