北大神经生物学神经系统对运动的调节专家讲座

CentralNervousSystemControlofMovementXING,GUOGANG(邢国刚),MD.Ph.D.北京大学神经科学研究所NeuroscienceResearchInstitute,PekingUniversityEmailaddress:ggxing@1北大神经生物学神经系统对运动的调节第1页Introduction生命在于运动……运动是动物维系个体生存和种族繁衍基本功效之一2北大神经生物学神经系统对运动的调节第2页Howdoesacoordinatedmovementachieved?3北大神经生物学神经系统对运动的调节第3页Thementalbodyimageseemstobegeneratedbysomatosensory,proprioceptive,andvisualinputstotheposteriorparietalcortex(area5,area7)Abaseballpitcherplanningapitch…4北大神经生物学神经系统对运动的调节第4页Thehighestlevel－

strategyRepresentedbytheassociationareasofneocortexandbasalgangliaoftheforebrainIsconcernedwithstrategy:ThegoalofthemovementandthemovementstrategythatbestachievesthegoalThemotorcontrolhierarchyhavethreelevels5北大神经生物学神经系统对运动的调节第5页Themiddlelevel－tacticsRepresentedbythemotorcortexandcerebellumIsconcernedwithtacticsThesequencesofmusclecontractionsArrangedinspaceandtimeRequiredtosmoothlyandaccuratelyachievethestrategicgoalThemotorcontrolhierarchyhavethreelevels6北大神经生物学神经系统对运动的调节第6页Thelowestlevel－

execution

RepresentedbythebrainstemandspinalcordIsconcernedwithexecutionActionofthemotorneuronandinterneuronpoolsthatgeneratethegoal-directedmovementandmakeanynecessaryadjustmentsofpostureThemotorcontrolhierarchyhavethreelevels7北大神经生物学神经系统对运动的调节第7页Overview脊髓内“下运动神经元(Lowerneurons)”，除了受到脊髓内局部环路影响外，还受到大脑皮层运动区及脑干中许多“上运动神经元(Upperneurons)”支配和协调基底神经节和小脑则向那些上运动神经元提供某种感觉、认知或感性信息，使运动愈加准确和协调8北大神经生物学神经系统对运动的调节第8页

9北大神经生物学神经系统对运动的调节第9页SensorimotorcortexBasalgangliaCerebellumBrainstemSpinalcordInterneuron

-MotorneuronMotorunit(finalcommonpathway)Receptorsmuscle,skin,joint12345Theseprogramsareaccessed,executed,andmodifiedbydescendingcommandsfromthebrainThebrain’scommandandcontrolofthemotorprogramsinthespinalcordThemotorsystemconsistsofallourmusclesandtheneuronsthatcommandthemThespinalcordcontainscertainmotorprogramsforthegenerationofcoordinatedmovementsThemotorcontrolcanbedividedintotwoparts:Thespinalcord’scommandandcontrolofcoordinatedmusclecontraction10北大神经生物学神经系统对运动的调节第10页Part1

SpinalControlofMovement11北大神经生物学神经系统对运动的调节第11页Introduction“runningaroundlikeachickenwithitsheadcutoff”

Therhythmicmovementscouldbeelicitedinthehindlegsofcatsanddogslongaftertheirspinalcordshadbeenseveredfromtherestofthecentralnervoussystem–CharlesSherington&GrahamBrown(English)Theimportanceofcircuitrywithinthespinalcordforthecoordinatedcontrolofmovements12北大神经生物学神经系统对运动的调节第12页Spinalcircuitry

controlofmovement13北大神经生物学神经系统对运动的调节第13页Spinalmotorneurons

Alphamotorneurons

Innervateskeletalmuscle(extrafusalmuscle)

Function:directlycommandmusclecontractGammamotorneurons

Innervatemusclespindle(intrafusalmuscle)

Function:regulatingthemusclespindleInterneurons

AllowscoordinatedmotorprogramstobegeneratedFinalcommonpathway(directlycommandmusclecontract)Compare:

UppermotorneuronsLowermotorneurons14北大神经生物学神经系统对运动的调节第14页TheLowerMotorNeurons

－AlphamotorneuronsAlphamotorneuronsaredirectlyresponsibleforthegenerationofforcebymuscleMotorunit:onealphamotor

neuronandallofthemusclefibersitinnervatescollectivelymakeupmotorunit,theelementarycomponentofmotorcontrolMotorneuronpool:Thecollectionofalphamotorneuronsthatinnervatesasinglemuscle15北大神经生物学神经系统对运动的调节第15页ThemotorunitisanalphamotorneuronandallofthemuscleAmotorunitandmotorneuronpoolThemotorneuronpoolisallofthealphamotorneuronsthatinnervateonemuscle16北大神经生物学神经系统对运动的调节第16页Muscleinnervationbylowermotorneurons30mixedspinalnervescervical1-8thoracic1-12lumbar1-5sacral1-5TheventralhornofthespinalcordcontainsmotorneuronsthatinnervateskeletalmusclefibersVentralroots+Dorsalroot=Spinalnerve17北大神经生物学神经系统对运动的调节第17页Thecervicalenlargementofthespinalcordcontainsthemotorneuronsthatinnervatethearmmuscles

Thelumbarenlargementcontainsneuronsthatinnervatethemusclesoftheleg

支配上肢神经元集群位于颈膨大处，支配下肢则在腰膨大处ThedistributionofmotorneuronsinthespinalcordThemotorneuronsthatinnervatedistalandproximalmusculaturearefoundmainlyinthecervicalandlumbar-sacralsegmentsofthespinalcordWhereasthoseinnervatingaxialmusculaturearefoundatalllevelsSegmentsC3-T1haveaswollenventralhornthatinnervateskeletalmusculatureinarmsSegmentsL1-S3haveaswollenventralhornthatinnervateskeletalmusculatureinlegs18北大神经生物学神经系统对运动的调节第18页Motorneuronscontrollingflexorsliedorsaltothosecontrollingextensors

Motorneuronscontrollingaxialmusclesliemedialtothosecontrollingdistalmuscles支配躯干部肌肉神经元位于脊髓前角灰质最内侧，由此向外排列神经元则支配肢体由近及远分布肌肉Thedistributionoflowermotorneuronsintheventralhorn19北大神经生物学神经系统对运动的调节第19页Muscleweaknessandparalysis－所支配骨骼肌瘫痪、肌张力下降、腱反射消失(软瘫)肌萎缩、纤维颤动或肌束颤动见于如肌萎缩侧索硬化症(amyotrophiclateralsclerosis,

ALS)：Selectivedamagetoalphamotorneurons(degeneration)－脊髓-运动神经元进行性溃变为主下运动神经元损伤表现20北大神经生物学神经系统对运动的调节第20页LouGehrigFarewellSpeech:"Fans,forthepasttwoweeksyouhavebeenreadingaboutthebadbreakIgot.YettodayIconsidermyselftheluckiestmanonthefaceofthisearth.……SoIcloseinsayingthatImayhavehadatoughbreak,butIhaveanawfullottolivefor."LouGehring,astarbaseballplayerwithNewYorkYankees,whodiedofALS(amyotrophiclateralsclerosis)in193621北大神经生物学神经系统对运动的调节第21页InputstoalphamotorneuronsThisinputisimportantfortheinitiationandcontrolofvoluntarymovementThisinputmaybeexcitatoryorinhibitoryandispartofthecircuitrythatgeneratesthespinalmotorprogramsThisinputprovidesfeedbackaboutmusclelength22北大神经生物学神经系统对运动的调节第22页SPINALCONTROLOFMOTORUNITSHowtheactivityofthemotorneuronisitselfcontrolled?23北大神经生物学神经系统对运动的调节第23页ReflexReceptorEffectorSpinalMotorNeuron(center)SkinMuscleJointMusclecontractionHigherCenterVoluntarymovementsNociceptivestimulusStretchmusclesPosturemaintenance24北大神经生物学神经系统对运动的调节第24页Themyotaticreflex(stretchreflex)Twotypesofmyotaticreflex

－TendonreflexandmuscletonusA.Tendonreflex

—快速牵拉肌腱而发生牵张反射Clinicapplication：了解脊髓不一样节段功效状态

reflexmothedCentralsiteeffect肘反射扣击肱二头肌肌腱颈5-7肘部屈曲膝反射扣击股四头肌肌腱腰2-4小腿伸直跟腱反射扣击跟腱腰5-骶2脚向足底方向屈曲单突触反射潜伏期很短，约0.7s只够一次突触传递时间延搁25北大神经生物学神经系统对运动的调节第25页+26北大神经生物学神经系统对运动的调节第26页B.Muscletonus

肌肉受到迟缓而连续牵拉而发生收缩－使骨骼肌能保持一定肌肉张力意义:维持身体姿势(posture)，而不表现显著动作表现：extensor(伸肌)和flexor(屈肌)都发生肌担心直立时，以伸肌担心为主，因重力作用于关节，使关节趋向弯曲，伸肌受到牵拉，引发肌担心反射，肌担心度增加以反抗关节屈曲因重力连续作用于关节，肌担心也就连续发生。使直立姿势得以维持多突触反射潜伏期较长，经过多个突触传递27北大神经生物学神经系统对运动的调节第27页

Musclespindles:ConsistsofspecializedskeletalmusclefibersInthismiddleregion,groupIa

sensoryaxonswraparoundthemusclefibersofthespindleThespindlesandtheirassociatedIaaxons,specializedforthedetectionofchangesinmusclelength(stretch):proprioceptorsandpropriceptionIaaxonsarethethickestmyelinatedaxonssotheyconductactionpotentialsveryrapidlyIaaxonsenterthespinalcordviathedorsalroots,branchrepeatedly,andformexcitatorysynapsesuponbothinterneuronsandalphamotorneuronsoftheventralhornsProprioceptionfrommusclespindlesMusclespindle

是一个可感受肌肉长度改变或感受牵拉刺激本体感受器梭内肌感受部装置位于中间,收缩成份位于两端,梭内肌收缩时或牵拉梭外肌时,感受装置对牵拉敏感性增高

28北大神经生物学神经系统对运动的调节第28页+29北大神经生物学神经系统对运动的调节第29页GammamotorneuronsExtrafusalfibersareinnervatedbyalphamotorneuronsIntrafusalfibersreceivetheirmotorinnervationbyanothertypeoflowermotorneuroncalledagammamotorneuronGammamotorneuronsinnervatetheintrafusalmusclefiberatthetwoendsofthemusclespindleActivationofthesefiberscausesacontractionofthetwopolesofthemusclespindle,therebypullingonthenon-contractileequatorialregionandkeepingtheIaafferentsactive30北大神经生物学神经系统对运动的调节第30页ThefunctionofgammamotorneuronsActivationofalphamotorneuronsshortenstheextrafusalmusclefibers.Ifthemusclespindlebecomesslack,itgoes“offtheair”andnolongerreportsthelengthofthemuscleActivationofgammamotorneuronscontractsthepolesofthespindle,keepingit“ontheair”31北大神经生物学神经系统对运动的调节第31页TheGammaloopChangingtheactivityofthegammamotorneuronschangesthesetpointofthemyotaticfeedbackloopTheGammaloopGammamotorneuron

intrafusalmusclefiberIaafferentalphamotorneuronextrafusalmusclefibersAlphaandgammamotorneuronsaresimultaneouslyactivatedbydescendingcommandsfromthebrain32北大神经生物学神经系统对运动的调节第32页ProprioceptionfromGolgitendonorgansGolgitendonorganActslikeastraingauge,itmonitorsmuscletension,ortheforceofcontractionLocatedatthejunctionofthemuscleandthetendonandareinnervatedbygroupIbsensoryaxonsthatareslightlysmallerthantheIaaxonsinnervatingthemusclespindles33北大神经生物学神经系统对运动的调节第33页GolgitendonorgansrespondtoincreasedtensiononthemuscleandtransmitthisinformationtothespinalcordviatypeIbsensoryafferents.Becausetheactivatedmuscledoesnotchangelength,theIaafferentsremainsilentinthisexample当肌肉等长收缩时,腱器官传入冲动频率,肌梭传入冲动频率不变;当肌肉等张收缩时,腱器官传入冲动频率不变,肌梭传入冲动频率Golgitendon

organslieinseriesbetweenthemusclefibersandtheirpointsofattachmentMusclespindlesarearrangedparalleltotheextrafusalfibers34北大神经生物学神经系统对运动的调节第34页TheIbafferentsenterthespinalcord,branchrepeatedly,andsynapseoninterneuronsintheventralhornSomeoftheseinterneuronsforminhibitoryconnectionswiththealphamotorneuronsinnervatingthesamemuscle.ThisisthebasisforthereversemyotaticreflexCircuitryofthereversemyotaticreflex＋-Musclespindlesituatedinparallelwiththemusclefibers,GolgitendonorgansaresituatedinseriesIaactivityfromthespindleencodesmusclelengthinformationWhileIbactivityfromtheGolgitendonorganencodesmuscletensioninformation腱器官是张力感受器,其传入冲动对同一肌肉运动神经元起抑制作用肌梭是长度感受器,其传入冲动对同一肌肉运动神经元起兴奋作用当肌肉被动牵拉时,二者传入冲动频率均：首先兴奋肌梭发动牵张反射,肌肉收缩,牵拉力大到一定程度,兴奋腱器官而抑制牵张反射牵张反射特点：反射弧简单，感受器和效应器在同一块肌肉35北大神经生物学神经系统对运动的调节第35页SignificanceofthereversemyotaticreflexInextremecircumstances,thisreflexarcprotectsthemusclefromoverloadThenormalfunctionistoregulatemuscletensionwithinanoptimalrangeAsmuscletension

increases,theinhibitionofthealphamotorneuronslowsmusclecontractionAsmuscletensionfalls,theinhibitionofthealphamotorneuronisreduced,andmusclecontractionincreasesThistypeofproprioceptivefeedbackisthoughttobeparticularlyimportantfortheproperexecutionoffinemotoracts,suchasthemanipulationoffragileobjectswiththehands,whichrequireasteadybutnottoopowerfulgrip36北大神经生物学神经系统对运动的调节第36页SpinalinterneuronsMostoftheinputtothealphamotorneuronscomesfrominterneuronsofthespinalcordInterneuronsreceivesynapticinputfromprimarysensoryaxons,descendingaxonsfromthebrain,andcollateralsoflowermotorneuronaxonsTheinterneuronsarethemselvesnetworkedtogetherinawaythatallowscoordinatedmotorprogramstobegeneratedinresponsetotheirmanyinputs37北大神经生物学神经系统对运动的调节第37页Reciprocalinhibitionofflexorsandextensorsofthesamejoint+++-InhibitoryinputContractionofonesetofmusclesaccompaniedbytherelaxationoftheantagonistmusclesiscalled

reciprocalinhibitionReciprocalinhibitionisalsousedbydescendingpathwaystoovercomethepowerfulmyotaticreflex38北大神经生物学神经系统对运动的调节第38页(A

&Cfibers)ExcitatoryinputFlexorreflex:usedtowithdrawalimbfromanaversivestimulus,suchasthewithdrawalofyourfootfromthethumbtackThepainfibersenteringthespinalcordbranchprofusedlyandactivateinterneuronsinseveralspinalsegments.Thesecellseventuallyexcite

thealphamotorneuronsthatcontrolalloftheflexormusclesoftheaffectedlimb(andinhibitoryinterneuronsarealsorecruitedtoinhibitthealphasthatcontroltheextensors)++++Circuitryofthepolysynapticflexorreflex39北大神经生物学神经系统对运动的调节第39页Circuitryofthecrossed-extensorreflexSpinalcordIpsilateralextensorsinhibitedContralateralextensorsactivated(contract)Ipsilateralflexorsactivated(contract)ContralateralflexorsinhibitedIpsilateralkneejointclosesuptoremovefootfromtackContralateralkneejointopensuptosupportgreaterweight40北大神经生物学神经系统对运动的调节第40页ThegenerationofspinalmotorprogramsforwalkingHeadlesschickens;behaviorAcompletetransectionofacat’sspinalcordatthemid-thoraciclevelleavesthehindlimbscapableofgeneratingcoordinatedwalkingmovementsWhenyouwalk,youalternatelywithdrawandextendyourtwolegs

Whatisthemechanismtocoordinatethetiming?Thiscouldbedescendingcommandsfromuppermotorneurons?No!Thiscontrolisexertedfromwithinthespinalcord?Yes!41北大神经生物学神经系统对运动的调节第41页42北大神经生物学神经系统对运动的调节第42页CentralpatterngeneratorswithinthespinalcordThecircuitforthecoordinatedcontrolofwalkingmustresidewithinthespinalcordIngeneral,circuitsthatgiverisetorhythmicmotoractivityarecalledcentralpatterngenerators

Howdoneuralcircuitsgeneraterhythmicpatternsofactivity?Thesimplestpatterngenerators,aresingleneuronswhosemembranepropertiesendowthemwithpacemakerproperties(pacemakerneurons)43北大神经生物学神经系统对运动的调节第43页Rhythmicactivityinaspinalinterneuron(Pacemakerneuron)SomeneuronsrespondtotheactivationofNMDAreceptorswithrhythmicdepolarization(a)Intherestingstate,theNMDAreceptorchannelsandthecalcium-activatedpotassiumchannelsareclosed(b)GlutamatecausestheNMDAreceptorstoopen,thecellmembranetodepolarize,andCa2+ionstoenterthecell(c)Theriseinintracellular[Ca2+]causestheCa2+-activatedpotassiumchannelstoopen.K+ionsleavetheneuron,hyperpolarizingthemembrane.ThehyperpolarizationallowsMg2+ionstoenterandclogtheNMDAchannel,arrestingtheflowofCa2+(d)As[Ca2+]falls,thepotassiumchannelsclose,resettingthemembraneforanotheroscillation44北大神经生物学神经系统对运动的调节第44页Apossiblecircuitforrhythmicalternatingactivity(walking)Walkingisinitiatedwhenasteadyinputexcitestwointerneuronsthatconnecttothemotorneuronscontrollingtheflexorsandextensors,respectively.Theinterneuronsrespondtoacontinuousinputbygeneratingburstsofoutputs.Theactivitiesofthetwointerneuronsalternatebecausetheyinhibiteachotherviaother(inhibitory)interneurons.Thus,aburstofactivityinoneinterneuronstronglyinhibitstheother(Pacemakerneuron)(Pacemakerneuron)45北大神经生物学神经系统对运动的调节第45页Part2

BrainControlofMovement46北大神经生物学神经系统对运动的调节第46页Howdoesthebraincommunicatewiththemotorneuronsofthespinalcord?47北大神经生物学神经系统对运动的调节第47页Overview来自高级中枢下行投射对脑干和脊髓环路运动控制主要影响随意运动和朝向目标运动发出下行投射中枢位于脑干一些部位以及大脑皮质运动区域脑干内两个主要结构－前庭核和网状结构对维持姿势很主要皮质主要运动区和次要运动区(运动前区)主要对运动进行计划并使运动高效率执行，皮质这种作用是经过对脑干内一些高级中枢以及脑干、脊髓中运动神经元和环路中间神经元控制来完成48北大神经生物学神经系统对运动的调节第48页Thedescendingspinaltractscontrolofmovement49北大神经生物学神经系统对运动的调节第49页ThedescendingspinaltractsControlpostureandunderbrainstemcontrolContolvoluntary

movementsofthedistalmusculatureandunderdirectcorticalcontrol50北大神经生物学神经系统对运动的调节第50页(Pyramidaltract)ControlfinemovementsofthearmsandfingersTheeffectsoflateralpathwaylesions(inmonkeys)－byDonaldLawrence&HansKuypers(inthelate1960s)TheLateralPathwaysXJoinincorticospinaltractinthelateralcolumnofthespinalcordTerminateinthedorsolateralregionoftheventralhornsandintermedialgraymatterWheremotorneuronsandinterneuronscontrolthedistalmuscles,particularlyflexorsInputfromfrontalcortexX51北大神经生物学神经系统对运动的调节第51页TheVentromedialPathwaysContainfourdescendingtracts

thevestibulospinaltractthetectospinaltractthepontinereticulospinaltractthemedullaryreticulospinaltract

Oringinateinthebrainstem

TerminateamongthespinalinterneuronsControllingproximalandaxialmusclesUsesensoryinformationaboutbalance,bodyposition,andthevisualenviromenttoreflexivelymaintainbalanceandbodyposture52北大神经生物学神经系统对运动的调节第52页Thevestibulospinalandtectospinaltractskeeptheheadbalanceontheshouldersasthebodymovesthroughspace,andtheyturntheheadinresponsetonewsensorystimuli(midbrain)RecivedirectinputfromretinaReciveprojectionsfromvisualcortex,aswellasafferentscarringsomatosensoryandauditoryinformationConstructamapofthewordaroundusThemotionofthefluidinthislabyrinth,whichaccompaniesmovementsofthehead,activateshaircellsthatsignalthevestibularnucleiviacranialnerveVIIIOne:ProjectsbilaterallydownthespinalcordandactivatesthecervicalspinalcircuitsthatcontrolneckandbackmusclesandguidheadmovementRelysensoryinformationfromthevestibularlabyrinthintheinnerearAnother:ProjectsipsilaterallyasfardownasthelumbarspinalcordIthelpsusmaintainanuprightandbalancedposturebyfacilitatingextensormotorneuronsofthelegsStimulationatonesiteinthismapLeadtoanorientingresponsethatdirectstheheadandeyestomove…53北大神经生物学神经系统对运动的调节第53页ThepontinereticulospinaltractenhancetheantigravityreflexesofthespinalcordByfacilitatingtheextensorsofthelowerlimbsHelpsmaintainastandingposturebyresistingtheeffectsofgravityThemedullaryreticulospinaltracthastheoppositeeffect:itliberatestheantigravitymusclesfromreflex

controlActivityinbothreticulospinaltractsiscontrolledbydescendingsignalsfromthecortexControlpostureofthetrunkandtheantigravitymusclesofthelimbs54北大神经生物学神经系统对运动的调节第54页AsummaryofthemajordescendingspinaltractsandtheirpointsoforiginMotorcortexdirectlyactivatesspinalmotorneuronsandliberatesthemfromreflexcontrolbycommunicatingwiththenucleioftheventromedialpathwaysSo,thecortexiskeyforvoluntarymovementandbehaviorTheventromedialpathwaysoriginatefromseveralregionsofthebrainstemandparticipatemainlyinthemaintenanceofpostureandcertainreflexmovementsInitiationofavoluntarymovements,requiresinstructionsthatdescendfromthemotorcortexalongthelateralpathways55北大神经生物学神经系统对运动的调节第55页ourattention56北大神经生物学神经系统对运动的调节第56页MotorCortexMotorCortex(Primarymotorcortex)(Premotorarea)(lateralregion)(Supplementarymotorarea)(medialregion)AreasofneocortexintimatelyinvolvedintheplanningandinstructionofvoluntarymovementThemotorcortexisacircuscribedregionofthefrontallobeArea4liesjustanteriortothecentralsulcusontheprecentralgyrusArea6liesjustanteriortoarea457北大神经生物学神经系统对运动的调节第57页58北大神经生物学神经系统对运动的调节第58页Asomatotopicmap

ofthehumanprecentralgyrus运动皮层对躯体运动调控特点：交叉性：但头面部肌肉支配是双侧性有精细功效定位：大致呈身体倒影:在4区内侧近中线部位是下肢代表区，向外侧依次为躯干、前臂、手指，最外侧靠近外侧沟处为面部和舌代表区头面代表区内部为正立运动精细部位其代表区大：如手指和面部59北大神经生物学神经系统对运动的调节第59页Area5PosteriorparietalcortexPrefrontalareas:inhumansarethoughttobeimportantforabstractthought,decisionmaking,andanticipatingtheconsequencesofactionArea6and4togethercontributemostoftheaxonstothedescendingcorticospinaltractArea6liesatthejunctionwheresignalsencodingwhatactionsaredesiredareconvertedintosignalsthatspecifyhowtheactionwillbecarriedoutPrefrontalareas,alongwiththeposteriorparietalcortex,representthehighestlevelsofthemotorcontrolhierarchy,wheredecisionsaremadeaboutwhatactionstotakeandtheirlikelyoutcomeBoththeprefrontalandtheparietalcortexsendaxonsthatconvergeoncorticalarea6Area5,receivesinputsfromprimarysomatosensorycorticalarea3,1,2Area7,receivesinputsfromhigher-ordervisualcorticalareas(MT)ThecontributionsofposteriorparietalandprefrontalcortexPrimarysomatosensorycorticalarea3,1,2Higher-ordervisualcorticalareas(MT)Area7PrefrontalareasForabstractthought,decisionmaking,andanticipatingtheconsequencesofactionArea6Area4Descendingcorticospinaltracts60北大神经生物学神经系统对运动的调节第60页Theinput-outputorganizationofM1PyramidalcellIncorticallayerV(Motorcortex,M1,Area4)Area6(anterior)Area3,1,2(posterior)Lowermotorneuronsofspinalcord

Thalamus(VLc)CerebellumBrainstemBasalgangliaThalamus(VLo)Somatosensoryinputs61北大神经生物学神经系统对运动的调节第61页Higher-ordermotorplanningUsingPET(positronemissiontomography)tomonitorchangesinthepatternsofcorticalactivationthataccompanyvoluntarymovementsWhenthesubjectswereaskedtoperformaseriesoffingermovementsfrommemory,thefollowingregionsofcortexshowedincreasedbloodflow:thesomatosensoryandposteriorparietalareas,partsoftheprefrontalcortex(area8),area6,andarea4－PlayaroleingeneratingtheintentiontomoveandconvertingthatintentionintoaplanofactionWhenthesubjectswereaskedonlytorehearsethemovementmentallywithoutactuallymovingthefinger,area6remainedactivebutarea4didnot－PerRolandandhiscolleagues(Danishneurologist)62北大神经生物学神经系统对运动的调节第62页Thedischargeofacellinthepremotorarea(PMA)beforeamovementArea6(SMAandPMA)playsanimportantroleintheplanningofmovement,particularlycomplexmovementsequencesofthedistalmusculature(a)Ready:Amonkeysitsbeforeapaneloflights.Thetaskistowaitforaninstructionstimulusthatwillinformhimothemovementrequiredtoreceiveajuicereward,thenperformthemovementwhenatriggerstimulusgoeson.TheactivityofaneuroninPMAisrecordedduringthetask(b)Set:theinstructionstimulusoccursatthetimeindicatedbytheupwardarrow,resultinginthedischargeoftheneuroninPMA(c)Go:shortlyafterthemovementisinitiated,thePMAcellceasesfiring63北大神经生物学神经系统对运动的调节第63页初级运动皮层和前运动区运动皮层(motorcortex)初级运动皮层(primarymotorarea)，即4区次级运动区或称前运动区辅助运动区(supplementarymotorarea)，位于初级运动皮层前面6区皮层内侧部分，大部分在大脑半球内侧面外侧前运动区(lateralpremotorarea)或称前运动皮层(premotorcortex)，位于6区外侧部分64北大神经生物学神经系统对运动的调节第64页皮层神经元运动皮层中神经细胞可分为两大类锥体细胞，特征是含有向皮层表面伸展顶树突。其轴突离开运动皮层到其它皮层或皮层下结构，是主要传出神经元非锥体细胞，包含星形细胞、篮状细胞和颗粒细胞，多数属于抑制性神经元65北大神经生物学神经系统对运动的调节第65页第Ⅵ层锥体细胞投射至丘脑，它们也有上行轴突侧支至皮层各层

皮层各层中锥体细胞投射第II、III层中锥体细胞投射至其它皮层区，位置较浅细胞投射至同侧皮层(如辅助运动区、前运动皮层、中央沟后感觉皮层)，较深投射至对侧皮层大多数向皮层下结构投射起源于第Ⅴ层锥体细胞，皮层脊髓神经元在第Ⅴ层深部，其中包含最大锥体细胞即Betz细胞。较浅第Ⅴ层锥体细胞则投射至延髓、桥脑和红核，最浅第Ⅴ层细胞投射至纹状体66北大神经生物学神经系统对运动的调节第66页皮层脊髓束和皮层延髓束大脑皮层经过皮层脊髓束和皮层延髓束控制运动皮层延髓束终止于延髓颅神经运动核，控制面部肌肉活动皮层脊髓束则支配脊髓运动核，控制躯体肌肉活动67北大神经生物学神经系统对运动的调节第67页皮层脊髓束和皮层延髓束走行皮层脊髓束和皮层延髓束一起经内囊下行到中脑腹侧，分散地穿过桥脑核，在延髓集合成锥体继续下行至延髓和脊髓交界处，约3/4纤维交叉至对侧而在脊髓背外侧束下行，称为外侧皮层脊髓束，另1/4纤维不交叉而在脊髓腹侧下行，称为腹侧皮层脊髓束68北大神经生物学神经系统对运动的调节第68页皮层脊髓束和皮层延髓束走行外侧皮层脊髓束主要终止于脊髓腹角外侧运动神经元和中间区内中间神经元，腹侧皮层脊髓束则主要投射至双侧腹角腹内侧运动神经元和中间区内侧中间神经元，支配躯干中线肌肉和肢体近侧肌肉皮层延髓束终止于脑干颅神经感觉和运动核69北大神经生物学神经系统对运动的调节第69页

运动皮层经过两条独立通路分别影响脊髓运动神经元一条经过锥体束直接通路直达脊髓灰质外侧和内侧运动神经元一条间接通路，即经过红核和网状结构接替70北大神经生物学神经系统对运动的调节第70页皮层脊髓纤维和运动神经元联络皮层脊髓神经元对脊髓

运动神经元有直接突触联络，起到强烈直接兴奋性影响皮层脊髓神经元间接影响运动神经元皮层脊髓束主要功效是控制肢体远端肌肉活动，尤其是手指活动经过脑干神经元间接地控制脊髓运动神经元。在初级运动皮层、前运动皮层和辅助运动区，都有神经元投射至脑干网状脊髓神经元及其它下行神经元而间接影响脊髓运动神经元皮层脊髓神经元经过上颈段脊髓中脊髓固有神经元，再影响位于颈膨大中支配前臂肌肉运动神经元经过抑制性中间神经元以施加抑制性影响71北大神经生物学神经系统对运动的调节第71页次级运动区运动功效初级运动皮层主要和运动执行相关次级运动区主要与运动准备（策划）相关使用PET影像研究局部脑血流与运动关系：执行简单动作如单指按压弹簧，则4区(S1)手代表区血流增加；执行复杂动作如轮排手指，则辅助运动区(S2)血流亦增加；若只默想复杂动作，则仅有辅助运动区血流增加72北大神经生物学神经系统对运动的调节第72页次级运动区运动功效次级运动区是选择正确运动战略所必需和初级运动皮层相比，损毁次级运动区(前运动皮层、辅助运动区和后顶叶皮层区)引发更为复杂运动异常，主要影响制订正确运动策略能力一侧辅助运动区和前运动皮层被损毁后，猴不会使用对侧前臂绕过挡在前面透明塑料板，并经过侧面洞去取所看见食物，相反，猴总是试图直接去取食物而一再撞到塑料板上这种运动缺损和人前额叶联络皮层或后顶叶皮层受损时引发失用症(apraxia)相同。这种病人能正常进行简单运动，但丧失了做需要有次序地收缩肌肉较复杂动作能力，比如刷牙和梳头等73北大神经生物学神经系统对运动的调节第73页Thebasalgangliacontrolofmovement74北大神经生物学神经系统对运动的调节第74页基底神经节(basalganglia)是从端脑衍生一些皮层下神经核团总称，位于大脑两半球深部。基底神经节中与运动功效相关主要是纹状体(striatum)尾核与壳核是基底神经节主要输入核(inputnuclei)，苍白球内侧部、脚内核和黑质网状部是基底神经节主要输出核(outputnuclei)，后二者结构和机能也很相同75北大神经生物学神经系统对运动的调节第75页Asummaryoftheloopfromthecortextothebasalganlgliatothethalamusandbacktoarea6Cerebralcortex(SMA)CaudatenucleusPutamenNewStriatumGlobuspallidus(OldStriadum)StriadumThalamus(theventrallateralnucleus,VLo)Frontalcortexneuron(Input)(Output)纹状体主要传入冲动来自大脑皮层广泛区域(运动区、体感区、联合区、边缘区甚至顶叶)传出冲动经过丘脑返回皮层，主要是辅助运动区(supplementarymotorarea)和运动前皮层(premotorcortex)，而与脊髓没有直接联络76北大神经生物学神经系统对运动的调节第76页基底神经节与大脑皮层纤维联络，与运动相关主要为三条回路皮层

新纹状体(尾、壳核)

苍白球(内侧部)

丘脑

皮层皮层

新纹状体(尾、壳核)

苍白球(外)

丘脑底核

苍白球(内)

丘脑

皮层皮层

新纹状体(尾、壳核)

黑质

丘脑

皮层基底神经节与与大脑皮层之间主要回路联络77北大神经生物学神经系统对运动的调节第77页1.皮层

新纹状体

苍白球(内侧)

丘脑

皮层回路大脑皮层(包含运动区、体感区、联合区、边缘区甚至顶叶)

新纹状体(包含尾核和壳核，即纹状体输入核)

苍白球内侧部

丘脑(包含腹前核、腹外侧核、内侧背核和中央中核)

大脑皮层(主要是运动区和辅助运动区皮层)78北大神经生物学神经系统对运动的调节第78页2.皮层

新纹状体

苍白球(外)

丘脑底核

苍白球(内)

丘脑

皮层回路大脑皮层相当广泛区域

新纹状体

苍白球外侧部

丘脑底核

苍白球内侧部

丘脑

皮层运动区和运动前区79北大神经生物学神经系统对运动的调节第79页3.皮层

新纹状体

黑质

丘脑

皮层回路大脑皮层相当广泛区域(包含运动区、体感区、联合区、边缘区甚至顶叶)

新纹状体

黑质网状部

丘脑腹前核和腹外侧核

大脑皮层(运动区和辅助运动区)纹状体(尾壳核)

黑质间存在含有局部定位特征往返纤维联络从黑质致密部有纤维投向新纹状体，它组成多巴胺能神经元系统；但黑质除有纤维至上丘和脚桥被盖核外，没有其它向下投射纤维 所以，基底神经节运动功效是经过大脑皮层中与运动控制相关区域而间接实现80北大神经生物学神经系统对运动的调节第80页直接通路易化运动直接通路包含通路1和3从皮层到新纹状体(输入核)递质是谷氨酸，是兴奋性；从新纹状体到苍白球内侧部及黑质网状部(输出核)递质是GABA和P物质，是抑制性；从这些输出核到丘脑递质也是GABA，也是抑制性；再由丘脑返回到皮层辅助运动区，则是兴奋性。当皮层有兴奋冲动下行到纹状体输入核使它兴奋时，就会使输出核中抑制细胞抑制，从而激活(去抑制)了丘脑神经元，再经过辅助运动区和运动前区激活运动皮层和向脑干及脊髓投射神经元，从而起易化运动效果81北大神经生物学神经系统对运动的调节第81页间接通路抑制运动间接通路包含通路2从皮层到新纹状体(输入核)递质是谷氨酸，是兴奋性；从纹状体输入核到苍白球外侧部递质是GABA和脑啡肽，是抑制性；从苍白球外侧部到丘脑底核递质是GABA，也是抑制性；从丘脑底核到苍白球内侧部(输出核)递质是谷氨酸，是兴奋性；从苍白球内侧部到丘脑递质是GABA，抑制性；再由丘脑返回到皮层辅助运动区，则是兴奋