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CellularNeurobiologyNeuroscienceResearchInstitutePekingUniversityDepartmentofNeurobiologyPekingUniversityHealthScienceCenterAlbertCheung-HoiYU于常海北京大學神經科學研究所achy@第1页OneoftheCajal’smanydrawingsofBraincircuityTheletterslabelthedifferentelementsCajalidentifiedinanareaofthehumancerebralcortexthatcontrolsvoluntarymovement.第2页Neurons:Excitablecells–“wiring”“SignalSenders”Neuroglia:Support,Nurturing,InsulationCellularComponents第3页NerveCellsNeuronsNeuroglia第4页Cellbody(soma;perikaryon)Axon:onlyone(branchesarecollaterals;terminalsareendfeet)Dendrites:muchshorter;oneormorethanone;branchextensivelyintodendritictreesStructureofNeuronsAxonHillock(Axonalendfeet)第5页TheAxonandAxonCollaterals第6页CellBody(Soma):

LifeSupportProteinSynthesisSingleNucleus,RER(NisslBodies)Axon:LongestprocesstransmitsmessagesawayfromcellbodyDendrites:Multipleprocessesoffcellbody–receivemessagesNeuronsStructure&Function第7页

Neuronsaresimilartoothercellsinthebodyinsomewayssuchas:1.Neuronsaresurroundedbyamembrane.2.Neuronshaveanucleusthatcontainsgenes.3.Neuronscontain:

Whatareinsideofaneuron?NucleusNucleolusMicrofilaments/NeurotubulesEndoplasmicReticulum(ER)Mitochondria

GolgiApparatusNisslBodiesOthers第8页Dendrites:dendritetreeAxon:axonhillock(axonorigination)axonaltransportsysteminitialsegment(firstmyelinsheath)actionpotentialgenerationmyelinsheathAxonandDendrites第9页AxonsDendritesTakeinformationawayfromthecellbodyTakeinformationtothecellbodySmoothsurfaceRoughsurface(dendriticspines)Generallyonly1axonpercellUsuallymanydendritespercellNoribosomeHaveribosomesCanhavemyelinNomyelininsulationBranchfurtherfromthecellbodyBranchnearthecellbodyDifferencesbetweenAxonsandDendrites第10页NeuronClassificationbyShapeMultipolar:“multi-”manyprocessesMajority:Singleaxon,manydendrites(motorneuronandinterneuron)Bipolar:“bi-”2processes

Foundinsomesensoryorgans(retina,taste,smell,innerearneuron)

Unipolar(pseudo-unipolar):“uni-”1process(withbranches)Sensoryafferentneurons(dorsalrootganglia)第11页ClassificationofNeuronsbyMorphology第12页ClassificationofNeuronsbyAxonLengthGolgitypeINeuronsLongaxons(longestfromthecortextothetipofspinalcord,50-70cm)GolgitypeIINeuronsShortaxons(shortestaxonsterminateonlyafewmicronfromcellbody,interneurons)AmacrineNeuronsAnunusualcelltype,lackaxons第13页Sensoryneuron

fromreceptortoCNS;receivestimuliandtransmitafferentimpulsestoCNSInterneuronscommunicatingbetweenneurons;formcircuitsintheCNSMotorneuron

fromCNStoeffectorcells;deliverefferentimpulsesoutthroughthePNStotheeffectorstocarryouttheactionsdirectedbytheCNSFunctionalClassificationofNeuron第14页EXCITABLEMembrane:Abletoregulatethemovementofions(charges)acrossandalongmembraneSIGNALTRANSDUCTIONDONOTReplicate:Damagedcellscannotbereplaced!ImportantFeatures

of

Neurons第15页ActionPotential第16页FourFunctionalRegionsofModelNeurons第17页Impulsetransmission:

electricalchemicalMorphology:

axodendriticaxonsomaticaxoaxonicdendrodendriticClassificationofSynapses第18页synapse4VesiclesreleaseNeurotransmitters第19页Chemicalsynapse:presynapticknob(presynapticcomponent)synapticvesiclessynapticcleftpostsynapticmembrane(postsynapticcomponent)Electricalsynapse:gapjunctionsSynapseStructures第20页第21页

TypesofsynapseDis-tanceCytoplasmiccontinuityUltrastruct-uralcomponentAgentoftrans-missionSynapticdelayDirectionoftrans-missionElectrical3.5nmYesGap-junctionchannelIoncurrentVirtuallyabsentUsuallybidirectionalChemical20-40nmNoPresynapticvesicleandactivezone;postsynapticreceptorsChemicaltransmittersSignificant:atleast0.3ms;usually1-5msorlongerUni-directional

DistinguishingPropertiesofElectricalandChemicalSynapses第22页Atachemicalsynapse,neuronstransmitinformationacrossacleft.第23页SmallMoleculeNeurotransmitterSubstancesAcetylcholine(ACh);Dopamine(DA);Norepinephrine(NE);Serotonin(5-HT);HistamineAminoAcidsGamma-aminobutyricacid(GABA);Glycine;Glutamate;AspartateNeuroactivePeptides-partiallist!!Bradykinin;beta-endorphin;calcitonin;cholecystokinin;enkephalin;dynorphin;insulin;gastrin;substanceP;glucagon;secretin;vasopressin;oxytocin,etc.ListofSomeNeurotransmitters第24页Axonaltransport:

intracellularcommunicationBidirectionalmechanism:anterogradetransportretrogradetransportClassifiedbytransportrates:slowtransportsystem(0.2to1mm/day)fasttransportsystem(200to400mm/day)AxonalTransportSystems第25页HitchingaRideon“Retrorail”第26页MembranesoforganellesinvolvedinsynaptictransmissionarereturnedtothecellbodyforreuseordegradationNucleusCytoskeleton(Anterogradetransport))第27页第28页ComponentRate(mm/day)StructureandcompositionFasttransport

Anterograde200-400Smallvesiculotubularstructures,neurotransmitters;membraneproteinsandlipidsMitochondria50-100MitochondriaRetrograde200-300LysosomalvesiclesandenzymesSlowtransport

SCb2-8Microfilaments,metabolicenzymes,clathrincomplexSCa0.2-1NeurofilamentsandmicrotubulesMajorRateComponentsofAxonalTransport第29页1.Neuronshavespecializedprojectionscalleddendritesandaxons.Dendritestakeinformationtothecellbodyandaxonstakeinformationawayfromthecellbody2.Neuronscommunicatewitheachotherthroughanelectrochemicalprocess3.Neuronscontainsomespecializedstructures(likesynapses)andchemicals(likeneurotransmitters)4.NisslBodies

5.DONOTReplicate:Damagedcellscannotbereplaced!NeuronsdifferfromOtherCells第30页Neuron:Supportingcells:CNS:neuroglia(glia)PNS:SchwanncellsandsatellitecellsFunctions:physicalsupportelectricalinsulationmetabolicexchangeblood-brainbarrierCompositionofNervousTissue第31页TypesandFunctionsofGliaNameofGlialCellFunctionAstrocyte(Astroglia)Star-shapedcellsthatprovidephysicalandnutritionalsupportforneurons:1)cleanupbrain"debris";2)transportnutrientstoneurons;3)holdneuronsinplace;4)digestpartsofdeadneurons;5)regulatecontentofextracellularspaceMicrogliaLikeastrocytes,microgliadigestpartsofdeadneurons.Oligo-dendrogliaProvidetheinsulation(myelin)toneuronsinthecentralnervoussystem.SatelliteCellsPhysicalsupporttoneuronsintheperipheralnervoussystem.SchwannCellsProvidetheinsulation(myelin)toneuronsintheperipheralnervoussystem.第32页NeurogliaintheCNS第33页Abletoreplicate!ImportanceinnervoussystemfunctionisVASTLYunderestimated!Evidenceismounting:NurturingroleSignalingrole(Memory?)InflammationPainManymoretocome!Neuroglia:DistinguishingFeatures第34页PresenceoftightjunctionsbetweentheendothelialcellsOneofthenotablefeaturesofendothelialcellsincomparisontoothercellisthelackofpinocyticvesiclesSelectivepermeabilitytomoleculesbasedontheirmolecularweightandlipidsolubilityPresenceofspecificmarkersRichintwoenzymes:gammaglutamyltranspeptidase(GGTP)(foraminoacidtransport)andalkalinephosphatase(transportofphsopahteions)usedasmarkerforBBB.Others:glucosetransporter(GLUT-1);endothelialbarrierantigen(EBA;unknownfunction)andantigenrecognizedbytheMRCOX-47monoclonalantibody(importantforcell-to-celladhesion);transferrinreceptor(transportofferricions).PropertiesofBloodBrainBarriers第35页BBB第36页1.NeuronshaveTWO"processes"calledaxonsanddendrites.GlialcellsonlyhaveONE.2.NeuronsCANgenerateactionpotentials.GlialcellsCANNOT,however,dohavearestingpotential.3.NeuronsHAVEsynapsesthatuseneurotransmitters.GlialcellsdoNOThavechemicalsynapses.4.NeuronsdoNOTcontinuetodivide.GlialcellsDOcontinuetodivide.5.TherearemanyMORE(10-50timesmore)glialcellsinthebraincomparedtothenumberofneurons.

Gliaaredifferentfromneurons:第37页NerveCells第38页Neurons,Glia,ExtracellularSpace,andBlood第39页BidirectionalCommunicationPartnersintheCNSReceivingsignalsfromneighboringneurons

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