LeadingEdgeReviewTheSelf-TuningNeuron:SynapticScalingofExcitatorySynapsesGinaG.Turrigiano1,*1DepartmentofBiology,VolenCenterforComplexSystems,andNationalCenterforBehavioralGenomics,BrandeisUniversity,Waltham,MA02454,USA*Correspondence:turrigiano@brandeis.eduDOI10.1016/j.cell.2008.10.008Homeostaticsynapticscalingisaformofsynapticplasticitythatadjuststhestrengthofallofaneuron’sexcitatorysynapsesupordowntostabilizefiring.Currentevidencesuggeststhatneuronsdetectchangesintheirownfiringratesthroughasetofcalcium-dependentsensorsthatthenregulatereceptortraffickingtoincreaseordecreasetheaccumulationofglutamatereceptorsatsynapticsites.Additionalmechanismsmayallowlocalornetwork-widechangesinactivitytobesensedthroughparallelpathways,generatinganestedsetofhomeostaticmechanismsthatoperateoverdifferenttemporalandspatialscales.Introductionfiedinawiderangeofsystemsthatconformtothisdefini-Ifyouarelikeme,yourcarprobablyneedsatriptotheshop.tionofhomeostaticplasticity(DavisandBezprozvanny,2001;AmechanicwillspendhoursmuckingaboutunderthehoodMarderandPrinz,2003;Turrigiano,1999;TurrigianoandNel-andwillchargeyoualotofmoney,andforalittlewhileyourson,2004).Thisreviewfocusesononeformofhomeostaticcarwillbefine—until,inevitably,itneedstogobacktotheplasticitydisplayedbycentralglutamatergicneurons,calledshopagain.Incontrast,youhavemadeitthroughyoursynapticscaling,anditscellularandmolecularmechanisms.lifethusfarwithoutbringingyourbraininforatune-up.ApictureisbeginningtoemergeofhowacellularnegativefeedbacksystemunderthecontrolofneuronalSomehowtheunstablestuffofwhichwearecomposedactivityisimplemented.Understandingwhen,haslearnedthetrickofmaintainingstability.where,andhowhomeostaticplasticityoper-atesinthecentralnervoussystemislikelytogenerateimportantinsightsintohowcircuits—WalterCannon,TheWisdomoftheBodyadaptduringexperience-dependentplastic-ity,aswellasthegenesisofaberrantstates,Thisisremarkable,giventhatyourbrainisfarmorecomplexsuchasaddictionorepilepsy,thatinvolv