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Filename:HBP-PSD16.2StateoftheartreviewEPFL120125.docxProjectNumber:284941ProjectTitle:HumanBrainProject–PreparatoryStudyDeliverableType:PU–PublicDeliverableNumber:D16.2ContractualDateofDeliverytotheCEC:October31,2011ActualDateofDeliverytotheCEC:January25,2011TitleofDeliverable:StateoftheArtReviewWorkpackagescontributingtotheDeliverable:AllNatureoftheDeliverable:ReportEditor:R.Walker(EPFL)Author(s):A.Ailamaki(EPFL,CH),K.Amunds(FZJ,DE),A.Araque(CSIC,ES),D.Armstrong(U.Edinburgh,UK),J.Ashburner(UCLInstituteofNeurology,UK),O.Blanke(EPFL,CH),M.Bolten(U.Wuppertal,DE),A.Brice(HopitaldelaSalpetrière,France),N.Burgess(UniversityCollegeLondon,UK),P.Carloni,RWTHAachenUniversity,DE),S.Chandran(U.Edinburgh,UK),J-PChangeux(InstitutPasteur,FR),K.Dalamagkidis(TUM,DE),J.DeFelipe(U.P.Madrid,ES),G.Dehaene-Lamberz(CEA,FR),S.Dehaene(CEA,FR),A.Destexhe(CNRS,FR),P.delosRios(EPFL,CH),C.Devilliers(CHUV,CH),M.Diesmann(FZJ,DE),Y.Dudai(HUI,IL),NorbertEicker(FZJ,DE),K.Evers,UppsalaUniversity,SE),C.Fauteux(EPFL,CH),P.Fries(ESI,DE),T.Freund(HungarianNationalAcademyofSciences,HU),A.Frommer(U.Wuppertal,DE),S.Furber(U.Manchester,UK),W.Gerstner(EPFL,CH),M-OGewaltig(EPFL,CH),O.Gigliotta(ISTC-CNR,IT),S.Grant(U.Edinburgh,UK),S.Grillner(KarolinskaInstitute,SE),T.Heinis(EPFL,CH),B.Hentschel(RWTHAachen,DE),S.Hill(KarolinskaInstitute,SE),P.Jonas(IST,AT),D.Keller(EPFL,CH),J-RKing(CEA,FR),A.Kleinschmidt(CEA,FR),G.Page2of82Klinker(TUM,DE),A.Knoll(TUM,DE),J.Labarta(BSC,ES),D.Lester(U.ManchesterUK),E.Lindahl(U.Stockholm,SE),T.Lippert(FZJ,DE),P.Magistretti(EPFL,CH),R.Malach(WeizmannInstitute,IL),JFMangin(CEA,FR),H.Markram(EPFL,CH),KHMeier(UHEI,DE),A.Meyer-Lindenberg(MannheimCentralInstituteofMentalHealth,DE),O.Miglno(ISTC-CNR,IT),A.Mohammed,(KarolinskaInstitute,SE),A.Nieder(U.Tuebingen,DE),F.Noe(FreieUniversitätBerlin,DE),M.Orozco(IRB,ES),B.Orth(FZJ,DE),A.Pavone(U.Florence,IT),C.Ponting(U.Oxford,UK),N.Rose(KingsCollege,UK),F.Röhrbein(TUM,DE),E.Ros(ES),M.Sansom,(U.Oxford,UK),J.Schemmel(UHEI,DE),F.Schürmann(EPFL,CH),J.Shillcock(EPFL,CH),M.Sigman(U.BuenosAires,AR),M.Slater(U.Barcelona,ES),B.Stahl,(DeMontfordUniversity,UK),B.Thirion(CEA,FR),A.Thomson,(U.London,UK),A.Toga(UCLAMedicalSchool,USA),R.Trappl(OFAI,AT),A.Triller(INSERM,FR),P.VanderSmagt(DE),V.VanWassenhowe(CEA,FR),F.Vidal,(MaxPlanckInstitute,DE),C.Wacogne(CEA,FR),R.Walker(EPFL,CH),S.Wittmeier(TUM,DE),F.Wolf(GRS,DE),Abstract:TheHBP-PSispreparingaproposalforaFlagshipProject(“TheHumanBrainProject”)intheFETFlagshipProgram.Atthisstageinourwork,wehypothesizethattheprojectwillbeorganizedinelevenPillarsofActivity”,eachbringingtogetherresearchersinaspecificacademicdiscipline,relevanttotheoverallgoalsoftheproject.ThisreportprovidesapreliminarysurveyofthecurrentstateofresearchonthethemescoveredbythepillarsKeywordList:HumanBrainProject,flagship,stateoftheart,literaturereview,molecularneuroscience,cellularneuroscience,cognitiveneuroscience,theoreticalneuroscience,neuroinformatics,brainsimulation,medicalinformatics,highperformancecomputing,neuromorphiccomputing,neurorobotics,education,ethicsandsocietyPage3of82ExecutiveSummaryOverviewThisreportprovidesapreliminarysurveyofthecurrentstateoftheartonthethemescoveredbytheeleven“PillarsofActivity”intheHumanBrainProject.Foreachpillarofactivitywedescribetheareasofresearchthepillarwilladdressandsummarizethecurrentstateoftheart.MolecularneuroscienceGoalThegoaloftheMolecularNeurosciencepillaristocollectstrategicallyselecteddataonmolecularsystemsinanimalandhumanbraincellsandtointegratethedatainmolecularlevelmodelsofneurons,gliaandsynapses,makingitpossibletoconnectgenesandthegenometocellsandcelltypes,circuitsandphysiology,behavioranddisease.PreviousresearchThemolecularunderstandingofthenervoussystemfirstblossomedduringthe1990s-theDecadeoftheBrain.Duringthisperiod,technicalinnovationsmadeitpossible,forthefirsttime,toexplorethemolecularfoundationsofspecificbrainfunctions,whileprogressinhumangeneticsandhumangenomesequencinguncoverednumerousmutationsimplicatedindiseasesofthebrainToday,thepaceofdiscoverycontinuestoaccelerate.However,muchworkisstillrequiredtobridgethegapbetweenbasicbiologicalresearchinexperimentalorganismsandhumanmedicalgenomics.HBPsimulationandmodeling,togetherwithstudiesofthemolecularbiologyofthehumanbraincanhelptofillthisgap.Transcriptomicandproteomicmethodsoriginallydevelopedinexperimentalorganismshavematuredtoapointwheretheycanbeappliedtohumanbrainmaterial.Thetimeisripeforunprecedentedadvancesinunderstandingthemolecularbiologyofthehumanbrain.CellularneuroscienceGoalThegoaloftheCellularNeurosciencepillaristoobtainstrategicbiologicaldatafromanimalbrainsthatfillgapsinourcurrentknowledgeandtogeneratepredictivemodelsofhardtomeasurefeaturesofthebrain.PreviousresearchInformationinthebrainflowsthroughsynapsesinafinelyandhighlycomplexorganizednetwork,which,atfirstsight,appearstoocomplextounravelatanytimeintheforeseeablefuture.Characterizingtheconnectomeismadeevenmoredifficultbyinter-individualvariabilityinbrainsize,corticalthickness,andnumbersofcellsandbytheadditionaldi