神经生物学：运动和运动疾病课件.pptx

1、运动和运动疾病Movement and Movement Disorders 医学部神经科学研究所Motor System运动系统运动系统 躯体运动系统躯体运动系统（Somatic motor system 自主运动系统自主运动系统（autonomic nervous system/Visceral motor system）Motor System运动系统运动系统躯体运动系统躯体运动系统（Somatic motor system）：中枢神经系统中与运动控制有关结构的总称，包括大脑皮层、脑干、脊髓、基地神经节、小脑和外周躯体运动神经纤维。其作用是生成运动计划（plan）、编制运动程序（prog

2、ram），并向骨骼肌发出运动指令（command）,以引起骨骼肌的收缩活动而产生躯体运动。Somatic Motor System（躯体运动系统）（躯体运动系统）Three types of movement（三种类型的运动）The organization of movement（运动的等级组织）Neural structures involved in controlling movements（控制运动的神经结构）Types of Movements（运动类型）（运动类型）反射运动Reflexive movements：最简单和最基本的运动方式，很少受意识的影响，具有等级反应性的特征（反

3、应的幅度和速度与刺激强度有关）随意运动Voluntary movements：为了达到某种目的而指向一定目标的运动。节律性运动Rhythmic movements：介于反射运动和随意运动间的一类运动。比如呼吸、心跳等。The Organization of Movement（运动的等级组织）（运动的等级组织）Spinal motor neurons execute movement The brain stem modulates the action of spinal motor circuits The cerebral cortex modulates the action of mo

4、tor neurons in the brain stem and spinal cordNeural Structures Involved in Controlling Movement Spinal cord脊髓 Brain stem脑干 Cerebral motor cortex 运动皮层Control movementsNeural Structures Involved in Controlling Movement Spinal cord Brain stem Cerebral motor cortex Cerebellum小脑 Basal ganglion基底神经节Contro

5、l movementsmodulationSpinal Control of Movement运动的脊髓调控运动的脊髓调控Lower Motor Neurons（低位运动神经元）（低位运动神经元）Lower motor neuron:in ventral horn of spinal cordAlpha motor neurons（运动神经元）:Predominantly in spinal cord axons synapse on skeletal musclesGamma motor neurons（运动神经元）:Located among alpha motor neurons and

6、 innervate intrafusal fibers（梭内肌纤维）of skeletal musclesExtrafusal fibers（梭外肌纤维）:Innervated by alpha motor neuronsIntrafusal fibers（梭内肌纤维）:Innervated by gamma motor neuronsTwo Types of Muscle Fibers Extrafusal fibers（梭外肌纤维）:Innervated by alpha motor neurons Intrafusal fibers（梭内肌纤维）:Innervated by gamma

7、 motor neurons 肌索肌索（muscle spindle）:感受肌肉长度变化信息的感受装置Two Types of Muscle FibersAlpha Motor Neuron:A neuron whose axon forms synapses with extrafusal muscle fibers of a skeletal muscle:activation contracts the muscle fibers.Motor unit（运动单位）:Motor neuron and all the muscle fibers it innervates Motor neu

8、ron pool（运动神经元池）:All the motor neurons that innervate a single muscleLower Motor Neurons ALS:amyotrophic lateral sclerosis肌萎缩性侧索硬化症肌萎缩性侧索硬化症ALS is a progressive fatal disease caused by degeneration of lower motor neurons in the lateral horn of the spinal cord and upper motor neurons of the cerebral

9、cortex,resulting in progressive motor weaknessALS:amyotrophic lateral sclerosisLou GehrigALS:amyotrophic lateral sclerosisLou GehrigStephen Hawking Neuromuscular junctionExcitation-Contraction Couplingl Muscle Contraction Alpha motor neurons release ACh ACh produces large EPSP in muscle fiber EPSP e

10、vokes muscle action potential Action potential triggers Ca2+release Fiber contracts Ca2+reuptake Fiber relaxesExcitation-Contraction CouplingMyasthenia Gravis（重症肌无力）（重症肌无力）MG is characterized by weakness and fatigability of voluntary muscles,typically including the muscles of facial expression MG is

11、 an autoimmune disease.The immune system of afflicted individuals generates antibodies against the bodys own nicotinic Ach receptors Effective treatments include AChE inhibitors or suppression of the immune systemInputs to Alpha Motor NeuronsLower Motor Neurons Dorsal root ganglion input from muscle

12、 spindle.Provides feedback about muscle length.Upper motor neurons in the motor cortex and brain stem.Voluntary control of muscles.InterneuronsSpinal Control of Motor Units运动单位的脊髓控制运动单位的脊髓控制 Proprioception from muscle spindles来自肌索的本体感觉 Proprioception from Golgi tendon organs来自高尔基腱器官的本体感觉 Spinal inte

13、rneurons脊髓中间神经元lSensory feedback from muscle spindles-stretch receptorSpinal Control of Motor Unitsl Golgi Tendon OrgansAdditional proprioceptive input-acts like strain gauge-monitors muscle tensionSpinal Control of Motor Units高尔基腱器官：感受张力变化信息lSpinal InterneuronsSynaptic inputs to spinal interneurons

14、:Primary sensory axons Descending axons from brain Collaterals of lower motor neuron axons Other interneuronsSpinal Control of Motor Units小结 Spinal control of movementDifferent levels of analysisSensation and movement linked:Direct feedbackIntricate network of circuitsBrain Control of Movement运动的脑部控

15、制运动的脑部控制Descending Spinal Tracts（下行脊髓束）（下行脊髓束）Cerebral Motor Cortex（大脑运动皮层）（大脑运动皮层）运动皮层（Motor Cortex）：初级运动皮层、前运动皮层、辅助运动皮层Area 4 and area 6 of the frontal lobeDescending Spinal Tracts下行脊髓束下行脊髓束 Axons from brain descend along two major pathways Lateral Pathways外测通路Ventromedial Pathways腹内侧通路 The Latera

16、l PathwaysVoluntary movement-originates in cortex（皮层）Components Corticospinal tract(皮层脊髓束)Rubrospinal tract（红核脊髓束）Descending Spinal TractsThe Ventromedial Pathways Posture and locomotion-originates in brain stem（脑干）The Vestibulospinal tract（前庭脊髓束）:head balance,head turning The Tectospinal tract（顶盖脊髓

17、束）:orienting responseDescending Spinal TractsThe Basal Ganglia基底神经节基底神经节 Basal Ganglia:Selection and initiation of willed movements Basal Ganglia Motor CircuitInput pathway to basal ganglia:cerebral cortex and substantia nigraOutput pathway of basal ganglia:cortex and brain stemBasal Ganglia Disorde

18、rs Parkinsons disease(PD)Huntingtons disease(HD)Clinical Features of PDPathological Hallmarks of PDLoss of dopaminergic neurons in the substantia nigra pars compacta(SNpc)Nigrostriatal Pathway Deficits in PDNeuron,2003Loss of dopamine neurons in Parkinsons diseaseStriatumMotor CortexMotorThalamusPre

19、motorCortex+Glutamate-GABAGPeGPi/SNrSTNDopamineSNc+-XEtiology of Parkinsons Disease Environmental toxin hypothesis MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine):a neurotoxin precursor to MPP+,which causes permanent symptoms of Parkinsons disease by destroying dopaminergic neurons in the substan

20、tia nigra of the brain.Rotenone:pesticide 鱼藤酮 Paraquat:herbicide 百草枯 Maneb:fungicide 代森锰 Etiology of Parkinsons Disease Genetic hypothesis SNCA:encoding-synuclein PARK2:encoding the E3 ubiquitin ligase parkin PARK6:encoding PINK1,a mitochondrial kinase PARK7:encoding the protein DJ-1 PARK8:encoding

21、leucine-rich repeat kinase 2 (LRRK2)PARK9:encoding ATP13A2Further reading if you are interested in Parkinsons diseaseHuntingtons Disease Huntingtons disease.HD is a progressive neurodegenerative disorder caused by expansion of a CAG repeat coding for polyglutamine in the N terminus of the huntingtin

22、 protein.Polyglutamine(PolyQ)Repeat40 repeats in HDHuntingtons Disease Selective loss of indirect-pathway neurons in Huntingtons DiseaseStriatumMotor CortexMotorThalamusPremotorCortex+Glutamate-GABAGPeGPi/SNrSTNDopamineSNc+-XFunctionsInvolved in control of smooth and accurate movements Clumsy moveme

23、nt results from dysfunctionInvolved in control of eye-hand coordination,movement timing,posture Serves as a type of movement error detection and correction system Receives copy of motor neural signals sent from motor cortex to musclesInvolved in learning motor skillsThe CerebellumThe Cerebellum Cere

24、bellar lesions小脑损伤小脑损伤Ataxia（共济失调）:Uncoordinated and inaccurate movementsDyssynergia（痉挛）:Decomposition of synergistic multijoint movementsDysmetria（测距不准）:Overshoot or undershoot target Anatomy of the CerebellumThe CerebellumSummary Lower motor neurons were controlled by cerebral cortex and brain ste

25、m Basal ganglion and cerebellum modulate movements Disorders associated with movementsQuestions1.Cerebellum and basal ganglion control movements directly()2.Which of the following neural structures is not involved in controlling movements()A.spinal cord B.brain stem C.hypothalamus D.cerebral motor c

26、ortex3.Which of the following is not belong to the basal ganglion()A.caudate nucleus B.Putamen C.Globus pallidus D.amygdala4.Motor unit5.Motor neuron pool6.List the components of the lateral and ventromedial descending spinal pathways.Which type of movement does each path control?IntroductionMotor P

27、rogramsMotor system:Muscles and neurons that control musclesRole:Generation of coordinated movementsParts of motor control Spinal cord coordinated muscle contraction Brain activate motor programs in spinal cordThe Somatic Motor System Types of MusclesSmooth:digestive tract,arteries,related structure

28、sStriated:Cardiac(heart)and skeletal(bulk of body muscle mass)lTypes of Motor UnitsFast motor units:Rapidly fatiguing white fibers(Few mitochondria,anaerobic metabolism,contract and fatigue rapidly)Slow motor units:Slowly fatiguing red fibers(Large number of mitochondria and enzymes,slow to contract

29、,can sustain contraction)Lower Motor Neurons lGamma LoopKeeps spindle“on air”Changes set point of the myotatic feedback loop Additional control of alpha motor neurons and muscle contractionSpinal Control of Motor Units Excitatory InputCrossed-extensor reflex:Activation of extensor muscles and inhibi

30、tion of flexors on opposite sideSpinal Control of Motor Units Generating Spinal Motor Programs for WalkingCircuitry for walking resides in spinal cordRequires central pattern generatorsSpinal Control of Motor UnitsThe Motor Loop Through the Lateral Cerebellum Calibrated execution of planned,voluntar

31、y,multijoint movementsThe CerebellumThe Planning of Movement by the Cerebral Cortex The Contributions of Posterior Parietal and Prefrontal Cortex(Contd)Anterior frontal lobes:Abstract thought,decision making and anticipating consequences of action Area 6:Actions converted into signals specifying how

32、 actions will be performed Per Roland Monitored cortical activation accompanying voluntary movement(PET)Results supported view of higher order motor planning Example of the baseball pitcher Walking:Ventromedial pathways Ready to pitch Neocortex,ventromedial pathways Pitch signs and strategy Sensory

33、information engages parietal and prefrontal cortex and area 6Concluding RemarksConcluding Remarks Example of the baseball pitcher(Contd)Winds and throws Increased basal ganglia activity(initiation)SMA activity M1 activation Corticopontocerebellar pathways Cerebellum Cortical input to reticular forma

34、tion Release of antigravity muscles Lateral pathway engages motor neurons action The Motor Loop Through the Lateral Cerebellum Pontine nuclei Axons from layer V pyramidal cells in the sensorimotor cortex form massive projections to pons Corticopontocerebellar projection 20 times larger than pyramidal tractThe Cerebellum The Motor Loop Through the Lateral Cerebellum Cerebellum-“brain inside”Learning New motor programs created to ensure smooth movementThe Cerebellum