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CellularNeurobiologyCellularNeurobiologyNeuroscienceResearchInstitutePekingUniversityDepartmentofNeurobiologyPekingUniversityHealthScienceCenterAlbertCheung-HoiYU于常海于常海北京大學神經科學研究所北京大學神經科學研究所2021/3/29 星期一1OneoftheCajalsOneoftheCajalsmanydrawingsofmanydrawingsofBraincircuityBraincircuityTheletterslabelthedifferentelementsCajalidentifiedinanareaofthehumancerebralcortexthatcontrolsvoluntarymovement.2021/3/29 星期一2Neurons:Excitablecells“wiring”“SignalSenders”Neuroglia:Support,Nurturing,InsulationCellularComponentsCellularComponents2021/3/29 星期一3NerveCellsNerveCellsNeuronsNeuroglia2021/3/29 星期一4Cellbody(soma;perikaryon)Axon:onlyone(branchesarecollaterals;terminalsareendfeet)Dendrites:muchshorter;oneormorethanone;branchextensivelyintodendritictreesStructureofNeuronsStructureofNeuronsAxonHillock(Axonalendfeet)2021/3/29 星期一5TheAxonTheAxonandAxonandAxonCollateralsCollaterals2021/3/29 星期一6CellBody(Soma):LifeSupportProteinSynthesisSingleNucleus,RER(NisslBodies)Axon:LongestprocesstransmitsmessagesawayfromcellbodyDendrites:MultipleprocessesoffcellbodyreceivemessagesNeuronsNeuronsStructure&FunctionStructure&Function2021/3/29 星期一7Neuronsaresimilartoothercellsinthebodyinsomewayssuchas:1.Neuronsaresurroundedbyamembrane.2.Neuronshaveanucleusthatcontainsgenes.3.Neuronscontain:Whatareinsideofaneuron?Whatareinsideofaneuron?NucleusNucleolusMicrofilaments/NeurotubulesEndoplasmicReticulum(ER)MitochondriaGolgiApparatusNisslBodiesOthers2021/3/29 星期一8Dendrites:dendritetreeAxon:axonhillock(axonorigination)axonaltransportsysteminitialsegment(firstmyelinsheath)actionpotentialgenerationmyelinsheathAxonandDendritesAxonandDendrites2021/3/29 星期一9AxonsDendritesTakeinformationawayfromthecellbodyTakeinformationtothecellbodySmoothsurfaceRoughsurface(dendriticspines)Generallyonly1axonpercellUsuallymanydendritespercellNoribosomeHaveribosomesCanhavemyelinNomyelininsulationBranchfurtherfromthecellbodyBranchnearthecellbodyDifferencesbetweenAxonsandDendrites2021/3/29 星期一10NeuronClassificationbyShapeNeuronClassificationbyShapeMultipolar:“multi-”manyprocessesMajority:Singleaxon,manydendrites(motorneuronandinterneuron)Bipolar:“bi-”2processesFoundinsomesensoryorgans(retina,taste,smell,innerearneuron)Unipolar(pseudo-unipolar):“uni-”1process(withbranches)Sensoryafferentneurons(dorsalrootganglia)2021/3/29 星期一11ClassificationofClassificationofNeuronsbyNeuronsbyMorphologyMorphology2021/3/29 星期一12ClassificationofNeuronsClassificationofNeuronsbyAxonLengthbyAxonLength1.GolgitypeINeuronsLongaxons(longestfromthecortextothetipofspinalcord,50-70cm)2.GolgitypeIINeuronsShortaxons(shortestaxonsterminateonlyafewmicronfromcellbody,interneurons)3.AmacrineNeuronsAnunusualcelltype,lackaxons2021/3/29 星期一13SensoryneuronfromreceptortoCNS;receivestimuliandtransmitafferentimpulsestoCNSInterneuronscommunicatingbetweenneurons;formcircuitsintheCNSMotorneuronfromCNStoeffectorcells;deliverefferentimpulsesoutthroughthePNStotheeffectorstocarryouttheactionsdirectedbytheCNSFunctionalClassificationofNeuronFunctionalClassificationofNeuron2021/3/29 星期一14EXCITABLEMembrane:Abletoregulatethemovementofions(charges)acrossandalongmembraneSIGNAL TRANSDUCTIONDONOTReplicate:Damagedcellscannotbereplaced!ImportantFeaturesImportantFeatures ofof NeuronsNeurons2021/3/29 星期一15ActionActionPotentialPotential2021/3/29 星期一16FourFunctionalRegionsofModelNeuronsFourFunctionalRegionsofModelNeurons2021/3/29 星期一17Impulsetransmission:electricalchemicalMorphology:axodendriticaxonsomaticaxoaxonicdendrodendriticClassificationofSynapsesClassificationofSynapses2021/3/29 星期一18synapse4VesiclesreleaseNeurotransmitters2021/3/29 星期一19Chemicalsynapse:presynapticknob(presynapticcomponent)synapticvesiclessynapticcleftpostsynapticmembrane(postsynapticcomponent)Electricalsynapse:gapjunctionsSynapseStructuresSynapseStructures2021/3/29 星期一202021/3/29 星期一21 TypesofsynapseDis-tanceCytoplasmiccontinuityUltrastruct-uralcomponentAgentoftrans-missionSynapticdelayDirectionoftrans-missionElectrical3.5nmYesGap-junctionchannelIoncurrentVirtuallyabsentUsuallybidirectionalChemical20-40nmNoPresynapticvesicleandactivezone;postsynapticreceptorsChemicaltransmittersSignificant:atleast0.3ms;usually1-5msorlongerUni-directionalDistinguishingPropertiesofDistinguishingPropertiesofElectricalandChemicalSynapsesElectricalandChemicalSynapses2021/3/29 星期一22Atachemicalsynapse,neuronstransmitinformationacrossacleft.2021/3/29 星期一231.SmallMoleculeNeurotransmitterSubstancesAcetylcholine(ACh);Dopamine(DA);Norepinephrine(NE);Serotonin(5-HT);Histamine2.AminoAcidsGamma-aminobutyric acid(GABA);Glycine;Glutamate;Aspartate3.NeuroactivePeptides-partiallist!Bradykinin;beta-endorphin;calcitonin;cholecystokinin;enkephalin;dynorphin;insulin;gastrin;substance P;glucagon;secretin;vasopressin;oxytocin,etc.ListofSomeNeurotransmittersListofSomeNeurotransmitters2021/3/29 星期一24Axonaltransport:intracellularcommunicationBidirectionalmechanism:anterogradetransportretrogradetransportClassifiedbytransportrates:slowtransportsystem(0.2to1mm/day)fasttransportsystem(200to400mm/day)AxonalTransportSystemsAxonalTransportSystems2021/3/29 星期一25HitchingaRideon“Retrorail”2021/3/29 星期一26MembranesoforganellesinvolvedinsynaptictransmissionarereturnedtothecellbodyforreuseordegradationNucleusCytoskeleton(Anterogradetransport)2021/3/29 星期一272021/3/29 星期一28ComponentRate(mm/day)StructureandcompositionFasttransportAnterograde 200-400Smallvesiculotubularstructures,neurotransmitters;membraneproteinsandlipidsMitochondria50-100MitochondriaRetrograde 200-300LysosomalvesiclesandenzymesSlowtransportSCb2-8Microfilaments,metabolicenzymes,clathrincomplexSCa0.2-1NeurofilamentsandmicrotubulesMajorRateComponentsofAxonalTransportMajorRateComponentsofAxonalTransport2021/3/29 星期一291.Neuronshavespecializedprojectionscalleddendritesandaxons.Dendritestakeinformationtothecellbodyandaxonstakeinformationawayfromthecellbody2.Neuronscommunicatewitheachotherthroughanelectrochemicalprocess3.Neuronscontainsomespecializedstructures(likesynapses)andchemicals(likeneurotransmitters)4.NisslBodies5.DONOTReplicate:Damagedcellscannotbereplaced!NeuronsdifferfromOtherCellsNeuronsdifferfromOtherCells2021/3/29 星期一30Neuron:Supportingcells:CNS:neuroglia(glia)PNS:SchwanncellsandsatellitecellsFunctions:physicalsupportelectricalinsulationmetabolicexchangeblood-brainbarrierCompositionofNervousTissueCompositionofNervousTissue2021/3/29 星期一31TypesandFunctionsofGliaNameofGlialCellFunctionAstrocyte(Astroglia)Star-shapedcellsthatprovidephysicalandnutritionalsupportforneurons:1)cleanupbraindebris;2)transportnutrientstoneurons;3)holdneuronsinplace;4)digestpartsofdeadneurons;5)regulatecontentofextracellularspaceMicrogliaLikeastrocytes,microgliadigestpartsofdeadneurons.Oligo-dendrogliaProvidetheinsulation(myelin)toneuronsinthecentralnervoussystem.SatelliteCellsPhysicalsupporttoneuronsintheperipheralnervoussystem.SchwannCellsProvidetheinsulation(myelin)toneuronsintheperipheralnervoussystem.2021/3/29 星期一32NeurogliaNeurogliaintheCNSintheCNS2021/3/29 星期一33Abletoreplicate!ImportanceinnervoussystemfunctionisVASTLYunderestimated!Evidenceismounting:1.Nurturingrole2.Signalingrole(Memory?)3.Inflammation4.Pain5.Manymoretocome!Neuroglia:Neuroglia:DistinguishingFeaturesDistinguishingFeatures2021/3/29 星期一341.Presenceoftightjunctionsbetweentheendothelialcells2.Oneofthenotablefeaturesofendothelialcellsincomparisontoothercellisthelackofpinocyticvesicles3.Selectivepermeabilitytomoleculesbasedontheirmolecularweightandlipidsolubility4.PresenceofspecificmarkersRichintwoenzymes:gammaglutamyltranspeptidase(GGTP)(foraminoacidtransport)andalkalinephosphatase(transportofphsopahteions)usedasmarkerforBBB.1.Others:glucosetransporter(GLUT-1);endothelialbarrierantigen(EBA;unknownfunction)andantigenrecognizedbytheMRCOX-47monoclonalantibody(importantforcell-to-celladhesion);transferrinreceptor(transportofferricions).PropertiesofBloodBrainBarriersPropertiesofBloodBrainBarriers2021/3/29 星期一35BBBBBB2021/3/29 星期一361.NeuronshaveTWOprocessescalledaxonsanddendrites.GlialcellsonlyhaveONE.2.NeuronsCANgenerateactionpotentials.GlialcellsCANNOT,however,dohavearestingpotential.3.NeuronsHAVEsynapsesthatuseneurotransmitters.GlialcellsdoNOThavechemicalsynapses.4.NeuronsdoNOTcontinuetodivide.GlialcellsDOcontinuetodivide.5.TherearemanyMORE(10-50timesmore)glialcellsinthebraincomparedtothenumberofneurons.Gliaaredifferentfromneurons:Gliaaredifferentfromneurons:2021/3/29 星期一37NerveCellsNerveCells2021/3/29 星期一38Neurons,Glia,Neurons,Glia,ExtracellularSpace,ExtracellularSpace,andBloodandBlood2021/3/29 星期一39BidirectionalCommunicationPartnersBidirectionalCommunicationPartnersintheCNSintheCNSReceivingsignalsfromneighboringneuronsandrespondingtothemwithreleaseofneuroactivesubstancesExpressreceptorsforalmostallneurotransmittersandneuromodulatorsIncreaseofintracellularcalciumconcentrationMembranedepolarizationinastrocytesarecommonresponsestoneuralactivityMetabolicallycoupledtoneuralactivity2021/3/29 星期一40MetabolismofAstrocytesandtheirMetabolismofAstrocytesandtheirMetabolicCooperationwithNeuronsMetabolicCooperationwithNeuronsGlucoseAminoacidmetabolismEnzymes:glutaminesynthetase(glutamate-glutaminecycle);glycogenphosphorylatase(glycogenmobilization);pyruvatecarboxylase(anapleroticsynthesisofoxaloacetate);cysteinesulfinatedecarboxylase(synthesisoftaurine);glycinecleavagesystem,glycinemetabolism.2021/3/29 星期一41ThreeTypesofMetabolicThreeTypesofMetabolicCooperationofAstrocytesandCooperationofAstrocytesandNeuronsNeurons1.Supplyoftheenergysubstratelactatetoneurons2.Therecyclingofneuronalglutamatebytheglutamate-glutaminecycle3.Thesupplybyastrocytesofprecursorsforneuronalglutathione(GSH)synthesis2021/3/29 星期一42
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