神经生物学：9-运动和运动疾病

1、运动和运动疾病Movement and Movement DisordersMotor 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（program），并向骨骼肌

2、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（反应的

3、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 m

4、otor 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Contr

5、ol 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 neuron

6、s and 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）: Innervate

7、d by gamma 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 innerv

8、ates Motor neuron 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

9、of the cerebral 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

10、muscle fiber EPSP evokes 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

11、facial expression MG is 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 ga

12、nglion input from muscle 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 organ

13、s来自高尔基腱器官的本体感觉 Spinal interneurons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 InterneuronsSynapt

14、ic inputs to spinal interneurons: 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 circui

15、tsBrain Control of Movement运动的脑部控制运动的脑部控制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Ven

16、tromedial Pathways腹内侧通路 The Lateral 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 balan

17、ce, head turning The Tectospinal tract（顶盖脊髓束）: 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 gang

18、lia: cortex and brain stemBasal Ganglia Disorders 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 Par

19、kinsons diseaseStriatumMotor CortexMotorThalamusPremotorCortex+ 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 d

20、isease by destroying dopaminergic neurons in the substantia 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 mito

21、chondrial kinase PARK7: encoding the protein DJ-1 PARK8: encoding 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 CA

22、G repeat coding for polyglutamine in the N terminus of the huntingtin protein.Polyglutamine (PolyQ) Repeat40 repeats in HDHuntingtons Disease Selective loss of indirect-pathway neurons in Huntingtons DiseaseStriatumMotor CortexMotorThalamusPremotorCortex+ Glutamate- GABAGPeGPi/SNrSTNDopamineSNc+-XFu

23、nctionsInvolved in control of smooth and accurate movements Clumsy movement 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 t

24、o musclesInvolved in learning motor skillsThe CerebellumThe Cerebellum Cerebellar 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 Cerebell

25、umSummary Lower motor neurons were controlled by cerebral cortex and brain stem 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

26、controlling movements ( ) A. spinal cord B. brain stem C. hypothalamus D. cerebral motor cortex3. 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 vent

27、romedial descending spinal pathways. Which type of movement does each path control?Thank YouThank YouIntroductionMotor ProgramsMotor system: Muscles and neurons that control musclesRole: Generation of coordinated movementsParts of motor control Spinal cord coordinated muscle contraction Brain activa

28、te motor programs in spinal cordThe Somatic Motor System Types of MusclesSmooth: digestive tract, arteries, related structuresStriated: Cardiac (heart) and skeletal (bulk of body muscle mass)lTypes of Motor UnitsFast motor units: Rapidly fatiguing white fibers (Few mitochondria, anaerobic metabolism

29、, contract and fatigue rapidly)Slow motor units: Slowly fatiguing red fibers (Large number of mitochondria and enzymes, slow to contract, can sustain contraction)Lower Motor Neurons lGamma LoopKeeps spindle “on air” Changes set point of the myotatic feedback loop Additional control of alpha motor ne

30、urons and muscle contractionSpinal Control of Motor Units Excitatory InputCrossed-extensor reflex: Activation of extensor muscles and inhibition of flexors on opposite sideSpinal Control of Motor Units Generating Spinal Motor Programs for WalkingCircuitry for walking resides in spinal cordRequires c

31、entral pattern generatorsSpinal Control of Motor UnitsThe Motor Loop Through the Lateral Cerebellum Calibrated execution of planned, voluntary, 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 actions will be performed