北大神经生物学7神经系统对运动的调节课件

1、Central Nervous System Control of MovementXING, GUOGANG(邢国刚), MD. Ph.D.北京大学 神经科学研究所Neuroscience Research Institute, Peking UniversityEmail address: 1Introduction生命在于运动运动是动物维系个体生存和种族繁衍的基本功能之一2How does a coordinated movement achieved ?3The mental body image seems to be generated by somatosensory, prop

2、rioceptive, and visual inputs to the posterior parietal cortex (area 5, area 7)A baseball pitcher planning a pitch4The highest level strategyRepresented by the association areas of neocortex and basal ganglia of the forebrainIs concerned with strategy: The goal of the movement and the movement strat

3、egy that best achieves the goalThe motor control hierarchy have three levels5The lowest level execution Represented by the brain stem and spinal cord Is concerned with execution Action of the motor neuron and interneuron pools that generate the goal-directed movement and make any necessary adjustmen

4、ts of postureThe motor control hierarchy have three levels7Overview脊髓内的“下运动神经元(Lower neurons)”，除了受到脊髓内局部环路的影响外，还受到大脑皮层运动区及脑干中许多“上运动神经元(Upper neurons)”的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、认知或感性的信息，使运动更加精确和协调8SensorimotorcortexBasalgangliaCerebellumBrain stemSpinal cordInterneuron - MotorneuronMotor unit(fi

5、nal common pathway)Receptorsmuscle, skin, joint12345These programs are accessed, executed, and modified by descending commands from the brainThe brains command and control of the motor programs in the spinal cordThe motor system consists of all our muscles and the neurons that command themThe spinal

6、 cord contains certain motor programs for the generation of coordinated movements The motor control can be divided into two parts:The spinal cords command and control of coordinated muscle contraction10Part 1 Spinal Control of Movement11Introduction“running around like a chicken with its head cut of

7、f” The rhythmic movements could be elicited in the hind legs of cats and dogs long after their spinal cords had been severed from the rest of the central nervous systemCharles Sherington & Graham Brown (English) The importance of circuitry within the spinal cord for the coordinated control of moveme

8、nts12Spinal motor neurons Alpha motor neurons Innervate skeletal muscle (extrafusal muscle) Function: directly command muscle contractGamma motor neurons Innervate muscle spindle (intrafusal muscle) Function: regulating the muscle spindleInterneurons Allows coordinated motor programs to be generated

9、Final common pathway (directly command muscle contract)Compare: Upper motor neuronsLower motor neurons14The Lower Motor Neurons Alpha motor neuronsAlpha motor neurons are directly responsible for the generation of force by muscleMotor unit: one alpha motor neuron and all of the muscle fibers it inne

10、rvates collectively make up motor unit, the elementary component of motor controlMotor neuron pool: The collection of alpha motor neurons that innervates a single muscle15Muscle innervation by lower motor neurons30 mixed spinal nervescervical 1-8thoracic 1-12lumbar 1-5sacral 1-5The ventral horn of t

11、he spinal cord contains motor neurons that innervate skeletal muscle fibersVentral roots + Dorsal root = Spinal nerve17The cervical enlargement of the spinal cord contains the motor neurons that innervate the arm musclesThe lumbar enlargement contains neurons that innervate the muscles of the leg支配上

12、肢的神经元集群位于颈膨大处，支配下肢的则在腰膨大处The distribution of motor neurons in the spinal cordThe motor neurons that innervate distal and proximal musculature are found mainly in the cervical and lumbar-sacral segments of the spinal cordWhereas those innervating axial musculature are found at all levelsSegments C3-T

13、1 have a swollen ventral horn that innervate skeletal musculature in armsSegments L1-S3 have a swollen ventral horn that innervate skeletal musculature in legs18Motor neurons controlling flexors lie dorsal to those controlling extensors Motor neurons controlling axial muscles lie medial to those con

14、trolling distal muscles支配躯干部肌肉的神经元位于脊髓前角灰质最内侧，由此向外排列的神经元则支配肢体由近及远分布的肌肉The distribution of lower motor neurons in the ventral horn19Muscle weakness and paralysis所支配的骨骼肌瘫痪、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(amyotrophic lateral sclerosis, ALS)：Selective damage to alpha motor neurons(degeneration)脊

15、髓-运动神经元的进行性溃变为主下运动神经元的损伤表现20Lou Gehrig Farewell Speech:Fans, for the past two weeks you have been reading about the bad break I got. Yet today I consider myself the luckiest man on the face of this earth. So I close in saying that I may have had a tough break, but I have an awful lot to live for.Lou

16、 Gehring, a star baseball player with New York Yankees, who died of ALS ( amyotrophic lateral sclerosis) in 193621Inputs to alpha motor neuronsThis input is important for the initiation and control of voluntary movementThis input may be excitatory or inhibitory and is part of the circuitry that gene

17、rates the spinal motor programsThis input provides feedback about muscle length22ReflexReceptorEffectorSpinal Motor Neuron(center)SkinMuscleJointMuscle contractionHigherCenterVoluntary movementsNociceptive stimulusStretch musclesPosture maintenance24The myotatic reflex (stretch reflex)Two types of m

18、yotatic reflex Tendon reflex and muscle tonusA.Tendon reflex 快速牵拉肌腱而发生的牵张反射Clinic application：了解脊髓不同节段的功能状态 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25B. Muscle tonus 肌肉受到缓慢而持续的牵拉而发生的收缩 使骨骼肌能保持一定的肌肉张力 意义: 维持身体的姿势(posture)，而不表现明显的动作 表现：extensor(伸肌)和flexor(屈肌)都发生肌紧张直立时，以伸肌紧张为主，因重力作用于关节，使关节趋向弯曲， 伸肌受到牵拉，引起肌紧张反射，肌紧张

19、度增加以对抗关节屈曲 因重力持续作用于关节，肌紧张也就持续发生。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 Muscle spindles:Consists of specialized skeletal muscle fibersIn this middle region, group Ia sensory axons wrap around the muscle fibers of the spindleThe spindles and their associated Ia axons, specialized for the detection of changes

20、in muscle length (stretch): proprioceptors and propriceptionIa axons are the thickest myelinated axons so they conduct action potentials very rapidlyIa axons enter the spinal cord via the dorsal roots, branch repeatedly, and form excitatory synapses upon both interneurons and alpha motor neurons of

21、the ventral hornsProprioception from muscle spindlesMuscle spindle 是一种可感受肌肉长度变化或感受牵拉刺激的 本体感受器梭内肌感受部装置位于中间,收缩成分位于两端, 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+29Gamma motor neuronsExtrafusal fibers are innervated by alpha motor neuronsIntrafusal fibers receive their motor innervation by another type of lower mo

22、tor neuron called a gamma motor neuronGamma motor neurons innervate the intrafusal muscle fiber at the two ends of the muscle spindle Activation of these fibers causes a contraction of the two poles of the muscle spindle, thereby pulling on the non-contractile equatorial region and keeping the Ia af

23、ferents active30The function of gamma motor neuronsActivation of alpha motor neurons shortens the extrafusal muscle fibers. If the muscle spindle becomes slack, it goes “off the air” and no longer reports the length of the muscleActivation of gamma motor neurons contracts the poles of the spindle, k

24、eeping it “on the air”31The Gamma loopChanging the activity of the gamma motor neurons changes the set point of the myotatic feedback loopThe Gamma loopGamma motor neuron intrafusal muscle fiber Ia afferent alpha motor neuron extrafusal muscle fibersAlpha and gamma motor neurons are simultaneously a

25、ctivated by descending commands from the brain32Proprioception from Golgi tendon organsGolgi tendon organActs like a strain gauge, it monitors muscle tension, or the force of contractionLocated at the junction of the muscle and the tendon and are innervated by group Ib sensory axons that are slightl

26、y smaller than the Ia axons innervating the muscle spindles33Golgi tendon organs respond to increased tension on the muscle and transmit this information to the spinal cord via type Ib sensory afferents. Because the activated muscle does not change length, the Ia afferents remain silent in this exam

27、ple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Golgi tendon organs lie in series between the muscle fibers and their points of attachmentMuscle spindles are arranged parallel to the extrafusal fibers34The Ib afferents enter the spinal cord, branch repeatedly, and synapse on interneu

28、rons in the ventral hornSome of these interneurons form inhibitory connections with the alpha motor neurons innervating the same muscle. This is the basis for the reverse myotatic reflexCircuitry of the reverse myotatic reflex-Muscle spindle situated in parallel with the muscle fibers, Golgi tendon

29、organs are situated in seriesIa activity from the spindle encodes muscle length informationWhile Ib activity from the Golgi tendon organ encodes muscle tension information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的特

30、点： 反射弧简单，感受器和效应器在同一块肌肉35Significance of the reverse myotatic reflexIn extreme circumstances, this reflex arc protects the muscle from overloadThe normal function is to regulate muscle tension within an optimal rangeAs muscle tension increases, the inhibition of the alpha motor neuron slows muscle co

31、ntractionAs muscle tension falls, the inhibition of the alpha motor neuron is reduced, and muscle contraction increasesThis type of proprioceptive feedback is thought to be particularly important for the proper execution of fine motor acts, such as the manipulation of fragile objects with the hands,

32、 which require a steady but not too powerful grip36Spinal interneuronsMost of the input to the alpha motor neurons comes from interneurons of the spinal cordInterneurons receive synaptic input from primary sensory axons, descending axons from the brain, and collaterals of lower motor neuron axonsThe

33、 interneurons are themselves networked together in a way that allows coordinated motor programs to be generated in response to their many inputs37Reciprocal inhibition of flexors and extensors of the same joint+-Inhibitory inputContraction of one set of muscles accompanied by the relaxation of the a

34、ntagonist muscles is called reciprocal inhibitionReciprocal inhibition is also used by descending pathways to overcome the powerful myotatic reflex38(A & C fibers)Excitatory inputFlexor reflex: used to withdraw a limb from an aversive stimulus, such as the withdrawal of your foot from the thumbtackT

35、he pain fibers entering the spinal cord branch profusedly and activate interneurons in several spinal segments. These cells eventually excite the alpha motor neurons that control all of the flexor muscles of the affected limb (and inhibitory interneurons are also recruited to inhibit the alphas that

36、 control the extensors)+Circuitry of the polysynaptic flexor reflex39Circuitry of the crossed-extensor reflexSpinalcordIpsilateralextensorsinhibitedContralateralextensorsactivated(contract)Ipsilateralflexorsactivated(contract)ContralateralflexorsinhibitedIpsilateralknee jointcloses up to remove foot

37、from tackContralateralknee jointopens up to support greaterweight40The generation of spinal motor programs for walkingHeadless chickens; behaviorA complete transectionof a cats spinal cord at the mid-thoracic level leaves the hind limbs capable of generating coordinated walking movementsWhen you wal

38、k, you alternately withdraw and extend your two legs What is the mechanism to coordinate the timing?This could be descending commands from upper motor neurons? No!This control is exerted from within the spinal cord? Yes!4142Central pattern generators within the spinal cordThe circuit for the coordin

39、ated control of walking must reside within the spinal cordIn general, circuits that give rise to rhythmic motor activity are called central pattern generators How do neural circuits generate rhythmic patterns of activity?The simplest pattern generators, are single neurons whose membrane properties e

40、ndow them with pacemaker properties (pacemaker neurons)43Rhythmic activity in a spinal interneuron(Pacemaker neuron)Some neurons respond to the activation of NMDA receptors with rhythmic depolarization(a) In the resting state, the NMDA receptor channels and the calcium-activated potassium channels a

41、re closed(b) Glutamate causes the NMDA receptors to open, the cell membrane to depolarize, and Ca2+ ions to enter the cell(c) The rise in intracellular Ca2+ causes the Ca2+-activated potassium channels to open. K+ ions leave the neuron, hyperpolarizing the membrane. The hyperpolarization allows Mg2+

42、 ions to enter and clog the NMDA channel, arresting the flow of Ca2+(d) As Ca2+ falls, the potassium channels close, resetting the membrane for another oscillation44A possible circuit for rhythmic alternating activity (walking)Walking is initiated when a steady input excites two interneurons that co

43、nnect to the motor neurons controlling the flexors and extensors, respectively. The interneurons respond to a continuous input by generating bursts of outputs. The activities of the two interneurons alternate because they inhibit each other via other (inhibitory) interneurons. Thus, a burst of activ

44、ity in one interneuron strongly inhibits the other(Pacemaker neuron)(Pacemaker neuron)45Part 2 Brain Control of Movement46How does the brain communicate with the motor neurons of the spinal cord?47Overview来自高级中枢的下行投射对脑干和脊髓环路的运动控制主要影响随意运动和朝向目标的运动发出下行投射的中枢位于脑干某些部位以及大脑皮质的运动区域脑干内的两个主要结构前庭核和网状结构对维持姿势很重要皮

45、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，皮质的这种作用是通过对脑干内的某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的控制来完成的48The descending spinal tracts control of movement49The descending spinal tractsControl posture and under brain stem controlContol voluntary movements of the distal musculature and under direct cortical control50(P

46、yramidal tract)Control fine movements of the arms and fingersThe effects of lateral pathway lesions(in monkeys)by Donald Lawrence & Hans Kuypers (in the late 1960s)The Lateral PathwaysXJoin in corticospinal tract in the lateral column of the spinal cordTerminate in the dorsolateral region of the ven

47、tral horns and intermedial gray matterWhere motor neurons and interneurons control the distal muscles, particularly flexorsInput from frontal cortexX51The Ventromedial PathwaysContain four descending tracts the vestibulospinal tractthe tectospinal tractthe pontine reticulospinal tractthe medullary r

48、eticulospinal tract Oringinate in the brain stem Terminate among the spinal interneurons Controlling proximal and axial musclesUse sensory information about balance, body position, and the visual enviroment to reflexively maintain balance and body posture52The vestibulospinal and tectospinal tracts

49、keep the head balance on the shoulders as the body moves through space , and they turn the head in response to new sensory stimuli(midbrain)Recive direct input from retinaRecive projections from visual cortex, as well as afferents carring somatosensory and auditory informationConstruct a map of the

50、word around usThe motion of the fluid in this labyrinth, which accompanies movements of the head, activates hair cells that signal the vestibular nuclei via cranial nerve VIIIOne: Projects bilaterally down the spinal cord and activates the cervical spinal circuits that control neck and back muscles

51、and guid head movementRely sensory information from the vestibular labyrinth in the inner earAnother: Projects ipsilaterally as far down as the lumbar spinal cordIt helps us maintain an upright and balanced posture by facilitating extensor motor neurons of the legsStimulation at one site in this map

52、 Lead to an orienting response that directs the head and eyes to move53The pontine reticulospinal tract enhance the antigravity reflexes of the spinal cordBy facilitating the extensors of the lower limbsHelps maintain a standing posture by resisting the effects of gravityThe medullary reticulospinal

53、 tract has the opposite effect: it liberates the antigravity muscles from reflex controlActivity in both reticulospinal tracts is controlled by descending signals from the cortexControl posture of the trunk and the antigravity muscles of the limbs54A summary of the major descending spinal tracts and

54、 their points of originMotor cortex directly activates spinal motor neurons and liberates them from reflex control by communicating with the nuclei of the ventromedial pathwaysSo, the cortex is key for voluntary movement and behaviorThe ventromedial pathways originate from several regions of the bra

55、in stem and participate mainly in the maintenance of posture and certain reflex movementsInitiation of a voluntary movements, requires instructions that descend from the motor cortex along the lateral pathways55our attention56Motor CortexMotor Cortex(Primary motor cortex)(Premotor area) (lateral reg

56、ion)(Supplementary motor area) (medial region)Areas of neocortex intimately involved in the planning and instruction of voluntary movementThe motor cortex is a circuscribed region of the frontal lobeArea 4 lies just anterior to the central sulcus on the precentral gyrusArea 6 lies just anterior to a

57、rea 45758A somatotopic map of the human precentral gyrus运动皮层对躯体运动的调控特点：交叉性：但头面部肌肉的支配是双侧性的有精细的功能定位：大体呈身体倒影: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的运动精细部位其代表区大：如手指和面部59Area 5Posterior parietal cortexPrefrontal areas: in humans are thought to be important for abstract thought, decis

58、ion making, and anticipating the consequences of actionArea 6 and 4 together contribute most of the axons to the descending corticospinal tractArea 6 lies at the junction where signals encoding what actions are desired are converted into signals that specify how the action will be carried outPrefron

59、tal areas, along with the posterior parietal cortex , represent the highest levels of the motor control hierarchy, where decisions are made about what actions to take and their likely outcomeBoth the prefrontal and the parietal cortex send axons that converge on cortical area 6Area 5, receives input

60、s from primary somatosensory cortical area 3,1,2Area 7, receives inputs from higher-order visual cortical areas (MT)The contributions of posterior parietal and prefrontal cortexPrimary somatosensory cortical area 3,1,2Higher-order visual cortical areas (MT)Area 7Prefrontal areasFor abstract thought,