1、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 星期一1OneoftheCajalsOneoftheCajalsmanydrawingsofmanydrawingsofBraincircuityBraincircuityTheletterslabe
2、lthedifferentelementsCajalidentifiedinanareaofthehumancerebralcortexthatcontrolsvoluntarymovement.2021/3/29 星期一2Neurons:Excitablecells“wiring”“SignalSenders”Neuroglia:Support,Nurturing,InsulationCellularComponentsCellularComponents2021/3/29 星期一3NerveCellsNerveCellsNeuronsNeuroglia2021/3/29 星期一4Cellb
3、ody(soma;perikaryon)Axon:onlyone(branchesarecollaterals;terminalsareendfeet)Dendrites:muchshorter;oneormorethanone;branchextensivelyintodendritictreesStructureofNeuronsStructureofNeuronsAxonHillock(Axonalendfeet)2021/3/29 星期一5TheAxonTheAxonandAxonandAxonCollateralsCollaterals2021/3/29 星期一6CellBody(S
4、oma):LifeSupportProteinSynthesisSingleNucleus,RER(NisslBodies)Axon:LongestprocesstransmitsmessagesawayfromcellbodyDendrites:MultipleprocessesoffcellbodyreceivemessagesNeuronsNeuronsStructure&FunctionStructure&Function2021/3/29 星期一7Neuronsaresimilartoothercellsinthebodyinsomewayssuchas:1.Neuronsaresu
5、rroundedbyamembrane.2.Neuronshaveanucleusthatcontainsgenes.3.Neuronscontain:Whatareinsideofaneuron?Whatareinsideofaneuron?NucleusNucleolusMicrofilaments/NeurotubulesEndoplasmicReticulum(ER)MitochondriaGolgiApparatusNisslBodiesOthers2021/3/29 星期一8Dendrites:dendritetreeAxon:axonhillock(axonorigination
6、)axonaltransportsysteminitialsegment(firstmyelinsheath)actionpotentialgenerationmyelinsheathAxonandDendritesAxonandDendrites2021/3/29 星期一9AxonsDendritesTakeinformationawayfromthecellbodyTakeinformationtothecellbodySmoothsurfaceRoughsurface(dendriticspines)Generallyonly1axonpercellUsuallymanydendrite
7、spercellNoribosomeHaveribosomesCanhavemyelinNomyelininsulationBranchfurtherfromthecellbodyBranchnearthecellbodyDifferencesbetweenAxonsandDendrites2021/3/29 星期一10NeuronClassificationbyShapeNeuronClassificationbyShapeMultipolar:“multi-”manyprocessesMajority:Singleaxon,manydendrites(motorneuronandinter
8、neuron)Bipolar:“bi-”2processesFoundinsomesensoryorgans(retina,taste,smell,innerearneuron)Unipolar(pseudo-unipolar):“uni-”1process(withbranches)Sensoryafferentneurons(dorsalrootganglia)2021/3/29 星期一11ClassificationofClassificationofNeuronsbyNeuronsbyMorphologyMorphology2021/3/29 星期一12Classificationof
9、NeuronsClassificationofNeuronsbyAxonLengthbyAxonLength1.GolgitypeINeuronsLongaxons(longestfromthecortextothetipofspinalcord,50-70cm)2.GolgitypeIINeuronsShortaxons(shortestaxonsterminateonlyafewmicronfromcellbody,interneurons)3.AmacrineNeuronsAnunusualcelltype,lackaxons2021/3/29 星期一13Sensoryneuronfro
10、mreceptortoCNS;receivestimuliandtransmitafferentimpulsestoCNSInterneuronscommunicatingbetweenneurons;formcircuitsintheCNSMotorneuronfromCNStoeffectorcells;deliverefferentimpulsesoutthroughthePNStotheeffectorstocarryouttheactionsdirectedbytheCNSFunctionalClassificationofNeuronFunctionalClassification
11、ofNeuron2021/3/29 星期一14EXCITABLEMembrane:Abletoregulatethemovementofions(charges)acrossandalongmembraneSIGNAL TRANSDUCTIONDONOTReplicate:Damagedcellscannotbereplaced!ImportantFeaturesImportantFeatures ofof NeuronsNeurons2021/3/29 星期一15ActionActionPotentialPotential2021/3/29 星期一16FourFunctionalRegion
12、sofModelNeuronsFourFunctionalRegionsofModelNeurons2021/3/29 星期一17Impulsetransmission:electricalchemicalMorphology:axodendriticaxonsomaticaxoaxonicdendrodendriticClassificationofSynapsesClassificationofSynapses2021/3/29 星期一18synapse4VesiclesreleaseNeurotransmitters2021/3/29 星期一19Chemicalsynapse:presy
13、napticknob(presynapticcomponent)synapticvesiclessynapticcleftpostsynapticmembrane(postsynapticcomponent)Electricalsynapse:gapjunctionsSynapseStructuresSynapseStructures2021/3/29 星期一202021/3/29 星期一21 TypesofsynapseDis-tanceCytoplasmiccontinuityUltrastruct-uralcomponentAgentoftrans-missionSynapticdela
14、yDirectionoftrans-missionElectrical3.5nmYesGap-junctionchannelIoncurrentVirtuallyabsentUsuallybidirectionalChemical20-40nmNoPresynapticvesicleandactivezone;postsynapticreceptorsChemicaltransmittersSignificant:atleast0.3ms;usually1-5msorlongerUni-directionalDistinguishingPropertiesofDistinguishingPro
15、pertiesofElectricalandChemicalSynapsesElectricalandChemicalSynapses2021/3/29 星期一22Atachemicalsynapse,neuronstransmitinformationacrossacleft.2021/3/29 星期一231.SmallMoleculeNeurotransmitterSubstancesAcetylcholine(ACh);Dopamine(DA);Norepinephrine(NE);Serotonin(5-HT);Histamine2.AminoAcidsGamma-aminobutyr
16、ic 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 星期一24Axonaltrans
17、port:intracellularcommunicationBidirectionalmechanism:anterogradetransportretrogradetransportClassifiedbytransportrates:slowtransportsystem(0.2to1mm/day)fasttransportsystem(200to400mm/day)AxonalTransportSystemsAxonalTransportSystems2021/3/29 星期一25HitchingaRideon“Retrorail”2021/3/29 星期一26Membranesofo
18、rganellesinvolvedinsynaptictransmissionarereturnedtothecellbodyforreuseordegradationNucleusCytoskeleton(Anterogradetransport)2021/3/29 星期一272021/3/29 星期一28ComponentRate(mm/day)StructureandcompositionFasttransportAnterograde 200-400Smallvesiculotubularstructures,neurotransmitters;membraneproteinsandl
19、ipidsMitochondria50-100MitochondriaRetrograde 200-300LysosomalvesiclesandenzymesSlowtransportSCb2-8Microfilaments,metabolicenzymes,clathrincomplexSCa0.2-1NeurofilamentsandmicrotubulesMajorRateComponentsofAxonalTransportMajorRateComponentsofAxonalTransport2021/3/29 星期一291.Neuronshavespecializedprojec
20、tionscalleddendritesandaxons.Dendritestakeinformationtothecellbodyandaxonstakeinformationawayfromthecellbody2.Neuronscommunicatewitheachotherthroughanelectrochemicalprocess3.Neuronscontainsomespecializedstructures(likesynapses)andchemicals(likeneurotransmitters)4.NisslBodies5.DONOTReplicate:Damagedc
21、ellscannotbereplaced!NeuronsdifferfromOtherCellsNeuronsdifferfromOtherCells2021/3/29 星期一30Neuron:Supportingcells:CNS:neuroglia(glia)PNS:SchwanncellsandsatellitecellsFunctions:physicalsupportelectricalinsulationmetabolicexchangeblood-brainbarrierCompositionofNervousTissueCompositionofNervousTissue202
22、1/3/29 星期一31TypesandFunctionsofGliaNameofGlialCellFunctionAstrocyte(Astroglia)Star-shapedcellsthatprovidephysicalandnutritionalsupportforneurons:1)cleanupbraindebris;2)transportnutrientstoneurons;3)holdneuronsinplace;4)digestpartsofdeadneurons;5)regulatecontentofextracellularspaceMicrogliaLikeastroc
23、ytes,microgliadigestpartsofdeadneurons.Oligo-dendrogliaProvidetheinsulation(myelin)toneuronsinthecentralnervoussystem.SatelliteCellsPhysicalsupporttoneuronsintheperipheralnervoussystem.SchwannCellsProvidetheinsulation(myelin)toneuronsintheperipheralnervoussystem.2021/3/29 星期一32NeurogliaNeurogliainth
24、eCNSintheCNS2021/3/29 星期一33Abletoreplicate!ImportanceinnervoussystemfunctionisVASTLYunderestimated!Evidenceismounting:1.Nurturingrole2.Signalingrole(Memory?)3.Inflammation4.Pain5.Manymoretocome!Neuroglia:Neuroglia:DistinguishingFeaturesDistinguishingFeatures2021/3/29 星期一341.Presenceoftightjunctionsb
25、etweentheendothelialcells2.Oneofthenotablefeaturesofendothelialcellsincomparisontoothercellisthelackofpinocyticvesicles3.Selectivepermeabilitytomoleculesbasedontheirmolecularweightandlipidsolubility4.PresenceofspecificmarkersRichintwoenzymes:gammaglutamyltranspeptidase(GGTP)(foraminoacidtransport)an
26、dalkalinephosphatase(transportofphsopahteions)usedasmarkerforBBB.1.Others:glucosetransporter(GLUT-1);endothelialbarrierantigen(EBA;unknownfunction)andantigenrecognizedbytheMRCOX-47monoclonalantibody(importantforcell-to-celladhesion);transferrinreceptor(transportofferricions).PropertiesofBloodBrainBa
27、rriersPropertiesofBloodBrainBarriers2021/3/29 星期一35BBBBBB2021/3/29 星期一361.NeuronshaveTWOprocessescalledaxonsanddendrites.GlialcellsonlyhaveONE.2.NeuronsCANgenerateactionpotentials.GlialcellsCANNOT,however,dohavearestingpotential.3.NeuronsHAVEsynapsesthatuseneurotransmitters.GlialcellsdoNOThavechemic
28、alsynapses.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,ExtracellularS
29、pace,ExtracellularSpace,andBloodandBlood2021/3/29 星期一39BidirectionalCommunicationPartnersBidirectionalCommunicationPartnersintheCNSintheCNSReceivingsignalsfromneighboringneuronsandrespondingtothemwithreleaseofneuroactivesubstancesExpressreceptorsforalmostallneurotransmittersandneuromodulatorsIncreas
30、eofintracellularcalciumconcentrationMembranedepolarizationinastrocytesarecommonresponsestoneuralactivityMetabolicallycoupledtoneuralactivity2021/3/29 星期一40MetabolismofAstrocytesandtheirMetabolismofAstrocytesandtheirMetabolicCooperationwithNeuronsMetabolicCooperationwithNeuronsGlucoseAminoacidmetabol
31、ismEnzymes: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