神经生物学课件：运动和运动疾病2015

1、运动和运动疾病Movement and Movement Disorders,Motor System,Somatic motor system Visceral motor system/autonomic nervous system,Somatic Motor System,Three types of movement The organization of movement Neural structures involved in controlling movements,Types of Movements,Reflexive movements/反射运动：Reflexes a

2、re stereotyped responses to specific stimuli that are generated by simple neural circuits in the spinal cord or brain stem. Voluntary movements/随意运动：The movements that are under conscious control by the brain. Rhythmic movements/节律性运动：Movements that can be controlled voluntarily, but many such movem

3、ents differ from voluntary movements in that their timing and spatial organization is controlled autonomously by spinal or brain stem circuitry.,The Organization of Movement,Spinal motor neurons execute movement The brain stem modulates the action of spinal motor circuits The cerebral cortex modulat

4、es the action of motor neurons in the brain stem and spinal cord,Neural Structures Involved in Controlling Movement,Spinal cord Brain stem Cerebral motor cortex,Control movements,Neural Structures Involved in Controlling Movement,Spinal cord Brain stem Cerebral motor cortex Cerebellum Basal ganglion

5、,Control movements,modulation,Neural Structures Involved in Controlling Movement,Spinal cord Brain stem Cerebral motor cortex Cerebellum Basal ganglion,Control movements,modulation,Spinal Control of Movement,Lower Motor Neurons,Lower motor neuron: in ventral horn of spinal cord,Alpha motor neurons:

6、Predominantly in spinal cord axons synapse on skeletal muscles Gamma motor neurons: Located among alpha motor neurons and innervate intrafusal fibers of skeletal muscles,Extrafusal fibers: Innervated by alpha motor neurons Intrafusal fibers: Innervated by gamma motor neurons,Two Types of Muscle Fibe

7、rs,Alpha Motor Neuron: A neuron whose axon forms synapses with extrafusal muscle fibers of a skeletal muscle: activation contracts the muscle fibers. Motor unit: Motor neuron and all the muscle fibers it innervates Motor neuron pool: All the motor neurons that innervate a single muscle,Lower Motor N

8、eurons,Inputs to Alpha Motor Neurons,Lower Motor Neurons,Dorsal root ganglion input from muscle spindle. Provides feedback about muscle length. Upper motor neurons in the motor cortex and brain stem. Voluntary control of muscles. Interneurons,14,Monosynaptic Stretch Reflex a reflex in which a muscle

9、 contracts in response to its being quickly stretched; involves a sensory neuron and a motor neuron, with one synapse between them,15,ALS: amyotrophic lateral sclerosis,ALS is a progressive fatal disease caused by degeneration of lower motor neurons in the lateral horn of the spinal cord and upper m

10、otor neurons of the cerebral cortex, resulting in progressive motor weakness,ALS: amyotrophic lateral sclerosis,Lou Gehrig,ALS: amyotrophic lateral sclerosis,Lou Gehrig,Stephen Hawking,Neuromuscular junction,Excitation-Contraction Coupling,Muscle Contraction Alpha motor neurons release ACh ACh produ

11、ces large EPSP in muscle fiber EPSP evokes muscle action potential Action potential triggers Ca2+ release Fiber contracts Ca2+ reuptake Fiber relaxes,Excitation-Contraction Coupling,Myasthenia Gravis,MG is characterized by weakness and fatigability of voluntary muscles, typically including the muscl

12、es of 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 system,Spinal Control of Motor Units,Proprioception from muscle

13、 spindles, Golgi tendon organs, and joints Spinal interneurons Brain control of the motor units,Sensory feedback from muscle spindles - stretch receptor,Spinal Control of Motor Units,Golgi Tendon Organs Additional proprioceptive input - monitors muscle tension,Spinal Control of Motor Units,Proprioce

14、ption from the joints Proprioceptive axons in joint tissues Respond to angle, direction and velocity of movement in a joint Information from joint receptors: Combined with muscle spindle, Golgi tendon organs, skin receptors,Spinal Control of Motor Units,Spinal Interneurons Synaptic inputs to spinal

15、interneurons: Primary sensory axons Descending axons from brain Collaterals of lower motor neuron axons Other interneurons,Spinal Control of Motor Units,Inhibitory Input Reciprocal inhibition: Contraction of one muscle set accompanied by relaxation of antagonist muscle Example: Myotatic reflex,Spina

16、l Control of Motor Units,Excitatory Input Flexor reflex: Complex reflex arc used to withdraw limb from aversive stimulus,Spinal Control of Motor Units,Concluding Remarks,Spinal control of movement Different levels of analysis Sensation and movement linked: Direct feedback Intricate network of circui

17、ts,Brain Control of Movement,Introduction,The brain influences activity of the spinal cord Voluntary movements Hierarchy of controls Highest level: Strategy Middle level: Tactics Lowest level: Execution Sensorimotor system Sensory information used by all levels of the motor system,Summary,Descending

18、 Spinal Tracts,Descending Spinal Tracts,Axons from brain descend along two major pathways Lateral Pathways Ventromedial Pathways,The Lateral Pathways Voluntary movement - originates in cortex Components Corticospinal tract (pyramidal tract) Rubrospinal tract,Descending Spinal Tracts,The Ventromedial

19、 Pathways Posture and locomotion - originates in brain stem The Vestibulospinal tract: head balance, head turning The Tectospinal tract: orienting response,Descending Spinal Tracts,The Planning of Movement by the Cerebral Cortex,Motor Cortex Area 4 and area 6 of the frontal lobe,Motor Cortex Area 4

20、= “Primary motor cortex” or “M1” Area 6 = “Higher motor area” Lateral region Premotor area (PMA) Medial region Supplementary motor area (SMA) Motor maps in PMA and SMA Similar functions; different groups of muscles innervated,The Planning of Movement by the Cerebral Cortex,The Basal Ganglia,Basal Ga

21、nglia: Selection and initiation of willed movements,Basal Ganglia Motor Circuit,Input pathway to basal ganglia: cerebral cortex and substantia nigra Output pathway of basal ganglia: cortex and brain stem,Basal ganglia motor circuit: direct pathway,Striatum,Motor Cortex,Motor Thalamus,Premotor Cortex

22、,Glutamate,GABA,GPe,GPi/SNr,STN,Dopamine,SNc,+,Basal ganglia motor circuit: indirect pathway,Striatum,Motor Cortex,Motor Thalamus,Premotor Cortex,Glutamate,GABA,GPe,GPi/SNr,STN,Dopamine,SNc,-,Basal Ganglia Disorders,Parkinsons disease (PD) Huntingtons disease (HD),Clinical Features of PD,Pathologica

23、l Hallmarks of PD,Loss of dopaminergic neurons in the substantia nigra pars compacta(SNpc),Nigrostriatal Pathway Deficits in PD,Neuron, 2003,Etiology of Parkinsons Disease,Environmental toxin hypothesis MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine): a neurotoxin precursor to MPP+, which causes

24、 permanent symptoms of Parkinsons disease 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

25、parkin PARK6: encoding PINK1,a mitochondrial kinase PARK7: encoding the protein DJ-1 PARK8: encoding leucine-rich repeat kinase 2 (LRRK2) PARK9: encoding ATP13A2,Further reading if you are interested in Parkinsons disease,Huntingtons Disease,Huntingtons disease. HD is a progressive neurodegenerative

26、 disorder caused by expansion of a CAG repeat coding for polyglutamine in the N terminus of the huntingtin protein.,Polyglutamine (PolyQ) Repeat,40 repeats in HD,Huntingtons Disease,Functions Involved in control of smooth and accurate movements Involved in control of eye-hand coordination, movement timing, posture Serves as a type of movement error detection and correction System Involved in learning motor skills,The Cerebellum,The Cerebellum,Cerebellar lesions Ataxia/共济失调:小脑共济失调导致运动的随意性、姿势的稳定性、平衡性、准确性等方面的障碍，严重影响患者步态、日常生活活动能力。 Dys