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CellularNeurobiologyCellularNeurobiology神经生物学神经生物学-神经元和神经胶质细胞神经元和神经胶质细胞-神经元神经元OneoftheCajalsOneoftheCajalsmanydrawingsofmanydrawingsofBraincircuityBraincircuityTheletterslabelthedifferentelementsCajalidentifiedinanareaofthehumancerebralcortexthatcontrolsvoluntarymovement.Neurons:Excitablecells“wiring”“SignalSenders”Neuroglia:Support,Nurturing,InsulationCellularComponentsCellularComponentsNerveCellsNerveCellsNeuronsNeurogliaCellbody(soma;perikaryon)Axon:onlyone(branchesarecollaterals;terminalsareendfeet)Dendrites:muchshorter;oneormorethanone;branchextensivelyintodendritictreesStructureofNeuronsStructureofNeuronsAxonHillock(Axonalendfeet)TheAxonTheAxonandAxonandAxonCollateralsCollateralsCellBody(Soma):LifeSupportProteinSynthesisSingleNucleus,RER(NisslBodies)Axon:LongestprocesstransmitsmessagesawayfromcellbodyDendrites:MultipleprocessesoffcellbodyreceivemessagesNeuronsNeuronsStructure&FunctionStructure&FunctionNeuronsaresimilartoothercellsinthebodyinsomewayssuchas:1.Neuronsaresurroundedbyamembrane.2.Neuronshaveanucleusthatcontainsgenes.3.Neuronscontain:Whatareinsideofaneuron?Whatareinsideofaneuron?NucleusNucleolusMicrofilaments/NeurotubulesEndoplasmicReticulum(ER)MitochondriaGolgiApparatusNisslBodiesOthersDendrites:dendritetreeAxon:axonhillock(axonorigination)axonaltransportsysteminitialsegment(firstmyelinsheath)actionpotentialgenerationmyelinsheathAxonandDendritesAxonandDendritesAxonsDendritesTakeinformationawayfromthecellbodyTakeinformationtothecellbodySmoothsurfaceRoughsurface(dendriticspines)Generallyonly1axonpercellUsuallymanydendritespercellNoribosomeHaveribosomesCanhavemyelinNomyelininsulationBranchfurtherfromthecellbodyBranchnearthecellbodyDifferencesbetweenAxonsandDendritesNeuronClassificationbyShapeNeuronClassificationbyShapeMultipolar:“multi-”manyprocessesMajority:Singleaxon,manydendrites(motorneuronandinterneuron)Bipolar:“bi-”2processesFoundinsomesensoryorgans(retina,taste,smell,innerearneuron)Unipolar(pseudo-unipolar):“uni-”1process(withbranches)Sensoryafferentneurons(dorsalrootganglia)ClassificationofClassificationofNeuronsbyNeuronsbyMorphologyMorphologyClassificationofNeuronsClassificationofNeuronsbyAxonLengthbyAxonLength1.GolgitypeINeuronsLongaxons(longestfromthecortextothetipofspinalcord,50-70cm)2.GolgitypeIINeuronsShortaxons(shortestaxonsterminateonlyafewmicronfromcellbody,interneurons)3.AmacrineNeuronsAnunusualcelltype,lackaxonsSensoryneuronfromreceptortoCNS;receivestimuliandtransmitafferentimpulsestoCNSInterneuronscommunicatingbetweenneurons;formcircuitsintheCNSMotorneuronfromCNStoeffectorcells;deliverefferentimpulsesoutthroughthePNStotheeffectorstocarryouttheactionsdirectedbytheCNSFunctionalClassificationofNeuronFunctionalClassificationofNeuronEXCITABLEMembrane:Abletoregulatethemovementofions(charges)acrossandalongmembraneSIGNAL TRANSDUCTIONDONOTReplicate:Damagedcellscannotbereplaced!ImportantFeaturesImportantFeatures ofof NeuronsNeuronsActionActionPotentialPotentialFourFunctionalRegionsofModelNeuronsFourFunctionalRegionsofModelNeuronsImpulsetransmission:electricalchemicalMorphology:axodendriticaxonsomaticaxoaxonicdendrodendriticClassificationofSynapsesClassificationofSynapsessynapse4VesiclesreleaseNeurotransmittersChemicalsynapse:presynapticknob(presynapticcomponent)synapticvesiclessynapticcleftpostsynapticmembrane(postsynapticcomponent)Electricalsynapse:gapjunctionsSynapseStructuresSynapseStructures TypesofsynapseDis-tanceCytoplasmiccontinuityUltrastruct-uralcomponentAgentoftrans-missionSynapticdelayDirectionoftrans-missionElectrical3.5nmYesGap-junctionchannelIoncurrentVirtuallyabsentUsuallybidirectionalChemical20-40nmNoPresynapticvesicleandactivezone;postsynapticreceptorsChemicaltransmittersSignificant:atleast0.3ms;usually1-5msorlongerUni-directionalDistinguishingPropertiesofDistinguishingPropertiesofElectricalandChemicalSynapsesElectricalandChemicalSynapsesAtachemicalsynapse,neuronstransmitinformationacrossacleft.1.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.ListofSomeNeurotransmittersListofSomeNeurotransmittersAxonaltransport:intracellularcommunicationBidirectionalmechanism:anterogradetransportretrogradetransportClassifiedbytransportrates:slowtransportsystem(0.2to1mm/day)fasttransportsystem(200to400mm/day)AxonalTransportSystemsAxonalTransportSystemsHitchingaRideon“Retrorail”MembranesoforganellesinvolvedinsynaptictransmissionarereturnedtothecellbodyforreuseordegradationNucleusCytoskeleton(Anterogradetransport)ComponentRate(mm/day)StructureandcompositionFasttransportAnterograde 200-400Smallvesiculotubularstructures,neurotransmitters;membraneproteinsandlipidsMitochondria50-100MitochondriaRetrograde 200-300LysosomalvesiclesandenzymesSlowtransportSCb2-8Microfilaments,metabolicenzymes,clathrincomplexSCa0.2-1NeurofilamentsandmicrotubulesMajorRateComponentsofAxonalTransportMajorRateComponentsofAxonalTransport1.Neuronshavespecializedprojectionscalleddendritesandaxons.Dendritestakeinformationtothecellbodyandaxonstakeinformationawayfromthecellbody2.Neuronscommunicatewitheachotherthroughanelectrochemicalprocess3.Neuronscontainsomespecializedstructures(likesynapses)andchemicals(likeneurotransmitters)4.NisslBodies5.DONOTReplicate:Damagedcellscannotbereplaced!NeuronsdifferfromOtherCellsNeuronsdifferfromOtherCellsNeuron:Supportingcells:CNS:neuroglia(glia)PNS:SchwanncellsandsatellitecellsFunctions:physicalsupportelectricalinsulationmetabolicexchangeblood-brainbarrierCompositionofNervousTissueCompositionofNervousTissueTypesandFunctionsofGliaNameofGlialCellFunctionAstrocyte(Astroglia)Star-shapedcellsthatprovidephysicalandnutritionalsupportforneurons:1)cleanupbraindebris;2)transportnutrientstoneurons;3)holdneuronsinplace;4)digestpartsofdeadneurons;5)regulatecontentofextracellularspaceMicrogliaLikeastrocytes,microgliadigestpartsofdeadneurons.Oligo-dendrogliaProvidetheinsulation(myelin)toneuronsinthecentralnervoussystem.SatelliteCellsPhysicalsupporttoneuronsintheperipheralnervoussystem.SchwannCellsProvidetheinsulation(myelin)toneuronsintheperipheralnervoussystem.NeurogliaNeurogliaintheCNSintheCNSAbletoreplicate!ImportanceinnervoussystemfunctionisVASTLYunderestimated!Evidenceismounting:1.Nurturingrole2.Signalingrole(Memory?)3.Inflammation4.Pain5.Manymoretocome!Neuroglia:Neuroglia:DistinguishingFeaturesDistinguishingFeatures1.Presenceoftightjunctionsbetweentheendothelialcells2.Oneofthenotablefeaturesofendothelialcellsincomparisontoothercellisthelackofpinocyticvesicles3.Selectivepermeabilitytomoleculesbasedontheirmolecularweightandlipidsolubility4.PresenceofspecificmarkersRichintwoenzymes:gammaglutamyltranspeptidase(GGTP)(foraminoacidtransport)andalkalinephosphatase(transportofphsopahteions)usedasmarkerforBBB.Others:glucosetransporter(GLUT-1);endothelialbarrierantigen(EBA;unknownfunction)andantigenrecognizedbytheMRCOX-47monoclonalantibody(importantforcell-to-celladhesion);transferrinreceptor(transportofferricions).PropertiesofBloodBrainBarriersPropertiesofBloodBrainBarriersBBBBBB1.NeuronshaveTWOprocessescalledaxonsanddendrites.GlialcellsonlyhaveONE.2.NeuronsCANgenerateactionpotentials.GlialcellsCANNOT,however,dohavearestingpotential.3.NeuronsHAVEsynapsesthatuseneurotransmitters.GlialcellsdoNOThavechemicalsynapses.4.NeuronsdoNOTcontinuetodivide.GlialcellsDOcontinuetodivide.5.TherearemanyMORE(10-50timesmore)glialcellsinthebraincomparedtothenumberofneurons.Gliaaredifferentfromneurons:Gliaaredifferentfromneurons:NerveCellsNerveCellsNeurons,Glia,Neurons,Glia,ExtracellularSpace,ExtracellularSpace,andBloodandBloodBidirectionalCommunicationPartnersBidirectionalCommunicationPartnersintheCNSintheCNSReceivingsignalsfromneighboringneuronsandrespondingtothemwithreleaseofneuroactivesubstancesExpressreceptorsforalmostallneurotransmittersandneuromodulatorsIncreaseofintracellularcalciumconcentrationMembranedepolarizationinastrocytesarecommonresponsestoneuralactivityMetabolicallycoupledtoneuralactivityMetabolismofAstrocytesandtheirMetabolismofAstrocytesandtheirMetabolicCooperationwithNeuronsMetabolicCooperationwithNeuronsGlucoseAminoacidmetabolismEnzymes:glutaminesynthetase(glutamate-glutaminecycle);glycogenphosphorylatase(glycogenmobilization);pyruvatecarboxylase(anapleroticsynthesisofoxaloacetate);cysteinesulfinatedecarboxylase(synthesisoftaurine);glycinecleavagesystem,glycinemetabolism.ThreeTypesofMetabolicThreeTypesofMetabolicCooperationofAstrocytesandCooperationofAstrocytesandNeuronsNeurons1.Supplyoftheenergysubstratelactatetoneurons2.Therecyclingofneuronalglutamatebytheglutamate-glutaminecycle3.Thesupplybyastrocytesofprecursorsforneuronalglutathione(GSH)synthesis
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