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CellularNeurobiologyNeuroscienceResearchInstitutePekingUniversityDepartmentofNeurobiologyPekingUniversityHealthScienceCenterAlbertCheung-HoiYU于常海北京大學神經科學研究所achy@2021/10/101OneoftheCajal’smanydrawingsofBraincircuityTheletterslabelthedifferentelementsCajalidentifiedinanareaofthehumancerebralcortexthatcontrolsvoluntarymovement.2021/10/102Neurons:Excitablecells–“wiring”“SignalSenders”Neuroglia:Support,Nurturing,InsulationCellularComponents2021/10/103NerveCellsNeuronsNeuroglia2021/10/104Cellbody(soma;perikaryon)Axon:onlyone(branchesarecollaterals;terminalsareendfeet)Dendrites:muchshorter;oneormorethanone;branchextensivelyintodendritictreesStructureofNeuronsAxonHillock(Axonalendfeet)2021/10/105TheAxonandAxonCollaterals2021/10/106CellBody(Soma):

LifeSupportProteinSynthesisSingleNucleus,RER(NisslBodies)Axon:LongestprocesstransmitsmessagesawayfromcellbodyDendrites:Multipleprocessesoffcellbody–receivemessagesNeuronsStructure&Function2021/10/107

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

Whatareinsideofaneuron?NucleusNucleolusMicrofilaments/NeurotubulesEndoplasmicReticulum(ER)Mitochondria

GolgiApparatusNisslBodiesOthers2021/10/108Dendrites:dendritetreeAxon:axonhillock(axonorigination)axonaltransportsysteminitialsegment(firstmyelinsheath)actionpotentialgenerationmyelinsheathAxonandDendrites2021/10/109AxonsDendritesTakeinformationawayfromthecellbodyTakeinformationtothecellbodySmoothsurfaceRoughsurface(dendriticspines)Generallyonly1axonpercellUsuallymanydendritespercellNoribosomeHaveribosomesCanhavemyelinNomyelininsulationBranchfurtherfromthecellbodyBranchnearthecellbodyDifferencesbetweenAxonsandDendrites2021/10/1010NeuronClassificationbyShapeMultipolar:“multi-”manyprocessesMajority:Singleaxon,manydendrites(motorneuronandinterneuron)Bipolar:“bi-”2processes

Foundinsomesensoryorgans(retina,taste,smell,innerearneuron)

Unipolar(pseudo-unipolar):“uni-”1process(withbranches)Sensoryafferentneurons(dorsalrootganglia)2021/10/1011ClassificationofNeuronsbyMorphology2021/10/1012ClassificationofNeuronsbyAxonLengthGolgitypeINeuronsLongaxons(longestfromthecortextothetipofspinalcord,50-70cm)GolgitypeIINeuronsShortaxons(shortestaxonsterminateonlyafewmicronfromcellbody,interneurons)AmacrineNeuronsAnunusualcelltype,lackaxons2021/10/1013Sensoryneuron

fromreceptortoCNS;receivestimuliandtransmitafferentimpulsestoCNSInterneuronscommunicatingbetweenneurons;formcircuitsintheCNSMotorneuron

fromCNStoeffectorcells;deliverefferentimpulsesoutthroughthePNStotheeffectorstocarryouttheactionsdirectedbytheCNSFunctionalClassificationofNeuron2021/10/1014EXCITABLEMembrane:Abletoregulatethemovementofions(charges)acrossandalongmembraneSIGNALTRANSDUCTIONDONOTReplicate:Damagedcellscannotbereplaced!ImportantFeatures

of

Neurons2021/10/1015ActionPotential2021/10/1016FourFunctionalRegionsofModelNeurons2021/10/1017Impulsetransmission:

electricalchemicalMorphology:

axodendriticaxonsomaticaxoaxonicdendrodendriticClassificationofSynapses2021/10/1018synapse4VesiclesreleaseNeurotransmitters2021/10/1019Chemicalsynapse:presynapticknob(presynapticcomponent)synapticvesiclessynapticcleftpostsynapticmembrane(postsynapticcomponent)Electricalsynapse:gapjunctionsSynapseStructures2021/10/10202021/10/1021

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

DistinguishingPropertiesofElectricalandChemicalSynapses2021/10/1022Atachemicalsynapse,neuronstransmitinformationacrossacleft.2021/10/1023SmallMoleculeNeurotransmitterSubstancesAcetylcholine(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.ListofSomeNeurotransmitters2021/10/1024Axonaltransport:

intracellularcommunicationBidirectionalmechanism:anterogradetransportretrogradetransportClassifiedbytransportrates:slowtransportsystem(0.2to1mm/day)fasttransportsystem(200to400mm/day)AxonalTransportSystems2021/10/1025HitchingaRideon“Retrorail”2021/10/1026MembranesoforganellesinvolvedinsynaptictransmissionarereturnedtothecellbodyforreuseordegradationNucleusCytoskeleton(Anterogradetransport))2021/10/10272021/10/1028ComponentRate(mm/day)StructureandcompositionFasttransport

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

SCb2-8Microfilaments,metabolicenzymes,clathrincomplexSCa0.2-1NeurofilamentsandmicrotubulesMajorRateComponentsofAxonalTransport2021/10/10291.Neuronshavespecializedprojectionscalleddendritesandaxons.Dendritestakeinformationtothecellbodyandaxonstakeinformationawayfromthecellbody2.Neuronscommunicatewitheachotherthroughanelectrochemicalprocess3.Neuronscontainsomespecializedstructures(likesynapses)andchemicals(likeneurotransmitters)4.NisslBodies

5.DONOTReplicate:Damagedcellscannotbereplaced!NeuronsdifferfromOtherCells2021/10/1030Neuron:Supportingcells:CNS:neuroglia(glia)PNS:SchwanncellsandsatellitecellsFunctions:physicalsupportelectricalinsulationmetabolicexchangeblood-brainbarrierCompositionofNervousTissue2021/10/1031TypesandFunctionsofGliaNameofGlialCellFunctionAstrocyte(Astroglia)Star-shapedcellsthatprovidephysicalandnutritionalsupportforneurons:1)cleanupbrain"debris";2)transportnutrientstoneurons;3)holdneuronsinplace;4)digestpartsofdeadneurons;5)regulatecontentofextracellularspaceMicrogliaLikeastrocytes,microgliadigestpartsofdeadneurons.Oligo-dendrogliaProvidetheinsulation(myelin)toneuronsinthecentralnervoussystem.SatelliteCellsPhysicalsupporttoneuronsintheperipheralnervoussystem.SchwannCellsProvidetheinsulation(myelin)toneuronsintheperipheralnervoussystem.2021/10/1032NeurogliaintheCNS2021/10/1033Abletoreplicate!ImportanceinnervoussystemfunctionisVASTLYunderestimated!Evidenceismounting:NurturingroleSignalingrole(Memory?)InflammationPainManymoretocome!Neuroglia:DistinguishingFeatures2021/10/1034PresenceoftightjunctionsbetweentheendothelialcellsOneofthenotablefeaturesofendothelialcellsincomparisontoothercellisthelackofpinocyticvesiclesSelectivepermeabilitytomoleculesbasedontheirmolecularweightandlipidsolubilityPresenceofspecificmarkersRichintwoenzymes:gammaglutamyltranspeptidase(GGTP)(foraminoacidtransport)andalkalinephosphatase(transportofphsopahteions)usedasmarkerforBBB.Others:glucosetransporter(GLUT-1);endothelialbarrierantigen(EBA;unknownfunction)andantigenrecognizedbytheMRCOX-47monoclonalantibody(importantforcell-to-celladhesion);transferrinreceptor(transportofferricions).PropertiesofBloodBrainBarriers2021/10/1035BBB2021/10/10361.NeuronshaveTWO"processes"calledaxonsanddendrites.GlialcellsonlyhaveONE.2.NeuronsCANgenerateactionpotentials.GlialcellsCANNOT,however,dohavearestingpotential.3.NeuronsHAVEsynapsesthatuseneurotransmitters.GlialcellsdoNOThavechemicalsynapses.4.NeuronsdoNOTcontinuetodivide.GlialcellsDOcontinuetodivide.5.TherearemanyMORE(10-50timesmore)glialcellsinthebraincomparedtothenumberofneurons.

Gliaaredifferentfromneurons:2021/10/1037NerveCells2021/10/1038Neurons,Glia,ExtracellularSpace,andBlood2021/10/1039BidirectionalCommunicationPartnersintheCNSReceivingsignalsfromneighborin

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