神經(jīng)生物學：9-運動和運動疾病

1、運動和運動疾病Movement and Movement DisordersMotor System運動系統(tǒng)運動系統(tǒng) 軀體運動系統(tǒng)軀體運動系統(tǒng)（Somatic motor system 自主運動系統(tǒng)自主運動系統(tǒng)（autonomic nervous system/ Visceral motor system）Motor System運動系統(tǒng)運動系統(tǒng)軀體運動系統(tǒng)軀體運動系統(tǒng)（Somatic motor system）：中樞神經(jīng)系統(tǒng)中與運動控制有關結構的總稱，包括大腦皮層、腦干、脊髓、基地神經(jīng)節(jié)、小腦和外周軀體運動神經(jīng)纖維。其作用是生成運動計劃（plan）、編制運動程序（program），并向骨骼肌

2、發(fā)出運動指令（command）,以引起骨骼肌的收縮活動而產(chǎn)生軀體運動。Somatic Motor System（軀體運動系統(tǒng)）（軀體運動系統(tǒng)） Three types of movement （三種類型的運動） The organization of movement （運動的等級組織） Neural structures involved in controlling movements （控制運動的神經(jīng)結構） Types of Movements（運動類型）（運動類型） 反射運動Reflexive movements：最簡單和最基本的運動方式，很少受意識的影響，具有等級反應性的特征（反應的

3、幅度和速度與刺激強度有關） 隨意運動Voluntary movements：為了達到某種目的而指向一定目標的運動。 節(jié)律性運動Rhythmic movements：介于反射運動和隨意運動間的一類運動。比如呼吸、心跳等。The Organization of Movement（運動的等級組織）（運動的等級組織） 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腦干 Cerebral motor cortex 運動皮層Control movementsNeural Structures Involved in Controlling Movement Spinal cord Brain stem Cerebral motor cortex Cerebellum小腦 Basal ganglion基底神經(jīng)節(jié)Contr

5、ol movementsmodulationSpinal Control of Movement運動的脊髓調(diào)控運動的脊髓調(diào)控Lower Motor Neurons（低位運動神經(jīng)元）（低位運動神經(jīng)元） Lower motor neuron: in ventral horn of spinal cordAlpha motor neurons（運動神經(jīng)元）: Predominantly in spinal cord axons synapse on skeletal musclesGamma motor neurons（運動神經(jīng)元）: Located among alpha motor neuron

6、s and innervate intrafusal fibers （梭內(nèi)肌纖維）of skeletal musclesExtrafusal fibers（梭外肌纖維）: Innervated by alpha motor neuronsIntrafusal fibers（梭內(nèi)肌纖維）: Innervated by gamma motor neuronsTwo Types of Muscle Fibers Extrafusal fibers（梭外肌纖維）: Innervated by alpha motor neurons Intrafusal fibers（梭內(nèi)肌纖維）: Innervate

7、d by gamma motor neurons 肌索肌索（muscle spindle）:感受肌肉長度變化信息的感受裝置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（運動單位）: Motor neuron and all the muscle fibers it innerv

8、ates Motor neuron pool（運動神經(jīng)元池）: All the motor neurons that innervate a single muscleLower Motor Neurons ALS: amyotrophic lateral sclerosis肌萎縮性側索硬化癥肌萎縮性側索硬化癥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（重癥肌無力）（重癥肌無力） 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運動單位的脊髓控制運動單位的脊髓控制 Proprioception from muscle spindles來自肌索的本體感覺 Proprioception from Golgi tendon organ

13、s來自高爾基腱器官的本體感覺 Spinal interneurons脊髓中間神經(jīng)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高爾基腱器官：感受張力變化信息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小結 Spinal control of movementDifferent levels of analysisSensation and movement linked:Direct feedbackIntricate network of circui

15、tsBrain Control of Movement運動的腦部控制運動的腦部控制Descending Spinal Tracts（下行脊髓束）（下行脊髓束）Cerebral Motor Cortex（大腦運動皮層）（大腦運動皮層） 運動皮層（Motor Cortex）：初級運動皮層、前運動皮層、輔助運動皮層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外測通路Ven

16、tromedial Pathways腹內(nèi)側通路 The Lateral PathwaysVoluntary movement - originates in cortex（皮層）Components Corticospinal tract (皮層脊髓束) Rubrospinal tract（紅核脊髓束）Descending Spinal TractsThe Ventromedial Pathways Posture and locomotion - originates in brain stem（腦干） The Vestibulospinal tract（前庭脊髓束）: head balan

17、ce, head turning The Tectospinal tract（頂蓋脊髓束）: orienting responseDescending Spinal TractsThe Basal Ganglia基底神經(jīng)節(jié)基底神經(jīng)節(jié) 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 魚藤酮 Paraquat: herbicide 百草枯 Maneb: fungicide 代森錳 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小腦損傷小腦損傷Ataxia（共濟失調(diào)）: Uncoordinated and inaccurate movementsDyssynergia（痙攣）: Decomposition of synergistic multijoint movementsDysmetria（測距不準）: 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