The Cerebellum. Outline. Overview Structure (external & internal) Micro-circuitry of the cerebellum Cerebellum and motor learning
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1 The Cerebellum P.T Ji Jun Cheol Rehabilitation Center 1 HansarangAsan Hospital. Outline Overview Structure (external & internal) Micro-circuitry of the cerebellum Cerebellum and motor learning 2 1
2 Cerebellum Overview Little brain (Latin) 10% total volume of the brain (1.8 M long) But more than 50% neurons of the entire brain Control fine movement coordination, balance and muscle tone 3 Cerebellum Overview This sensory structure influences the motor systems by evaluating disparities between intention and action and by adjusting the operation of motor centers in the brainstem and cortex while a movement is in progress. Adjusts the operation of motor centers in the cortex and the brain stem while a movement is in progress. Damage to the cerebellum disrupts the spatial accuracy and temporal coordination of movement 4 2
3 Cerebellum Overview Basic circuit: Mossy, Parallel & climbing fibers etc.. Main descending system : Pontine & vestibulospinal system Corticospinal & rubrospinal system Cerebellar modification of movements: Extension vs flexion in stance and swing Vestibulo-ocular reflex Conditioned eye-blink response Cerebral cortical learning 5 Structure (external) The cerebellum is located dorsal to the brainstem, caudal to the occipital lobe of the cerebrum. 6 3
4 Structure (external) 7 Structure (external) Emboliform Globose nucleus 8 4
5 Structure (functional) 9 Structure (functional) Different regions of the cerebellar cortex receive input from different sources. 10 5
6 Structure (pathway) Inputs to the cbll 11 Structure (pathway) Outputs of the Cbll Superior cerebellar peduncle 12 6
7 Structure (Input & output division) 13 Functional Considerations (Vestibulocerebellum) semicircular canals (vestibular apparatus) Cortex Flocculonodualr Deep N. vsetibular nuclei(fastigial) Input Vestibular nuclei Output Vestibular nuclei, reticular nuclei Vestibulospinal and reticulospinal tract. Function Eye movement, posture, balacne(extensor) 14 7
8 Functional Considerations (Spinocerebellum) Cortex Vermis, paravermis Deep N. Interpose, Fastigial Input Spinal cord(trunk,limb) & Brain stem (auditory and vestibular information) Output via interposed N. to red nucleus (rubrospinal) ventrolateral thalamus (corticospinal) for limb musculature via fastigial N. for axial musculature Function posture, balance (extensor), body & limb movment, eye movement, 15 Functional Considerations (Cerebrocerebellum) Cortex Lateral hemisheres Deep N. Dentate N. Input Cerebral cortex (via pontine N.) Output via red nucleus and VL of thalamus, motor and premotor cortex. (rubrospinal T, cortricospinal T. Function planning of skilled, complex movements in hands 16 8
9
10 Structure (pathway summary) Functional Division (Anatomic Location) Vestibulocerebellum (flocculornodurar lobe) Spinocerebellum Vermal section Receives Input from Sends Output To Output reaches Lower Motor Neurons Via Vestibular apparatus Vestibular nuclei Spinal cord (from trunk) Vestibular nuclei Auditory and vestibular information(via brain stem nuclei) Vestibular nuclei (via fastigial n.) Vestibular nuclei Recticular nuclei(via fastigial nucleus) Motor cortex(via fasigial nucleu then thalamus) Vestibulospinal tracts and tracts that coordinate eyes and head movement Vestibulospinal tracts Recticulospinal tracts Medial corticospinal tract 19 Structure (pathway summary) Functional Division (Anatomic Location Spinocerebellum Paravermal section Cerebrocerebellum (lateral cerebellar hemispheres) Receives Input From Spinal cord (from limbs) Cerebral cortex (via pontine nuclei) Sends Output To Red nucleus(via globose and emboliform nulei) Motor cortex (via fastigial nucleus then thalamus) Motor and premotor cortises(via dentate nucleus and motor thalamus) Red nucleus Output reaches Lower Motor Neurons Via Rubrospinal Tract Lateral corticospinal tract Lateral corticospinal and corticobulbar tracts) Rubrospinal tract 20 10
11 Cerebellar Cortex Micro-circuitry of the cerebellum I. Molecular Layer Setellate Cell --- taurine (inhibitory) afferent: parallel fiber efferent: Purkinje cell dendrite Basket Cell ---- GABA (inhibitory) afferent: parallel fiber efferent: Purkinje cell soma Parallel Fiber granule cell axon Purkinje Cell Dendrite 21 Cerebellar Cortex Micro-circuitry of the cerebellum II. Purkinje Cell Layer Purkinje Cell -- 15,000,000 in number -- GABA (inhibitory) afferent: parallel fiber climbing fiber stellate cell basket cell efferent: deep cortical nuclei 22 11
12 Micro-circuitry of the cerebellum Cerebellar Cortex III. Granular Layer Granular Cell -- 50,000,000,000 in number -- glutamic acid (excitatory) afferent: mossy fiber efferent: Purkinje cell dendrite Golgi Cell -- GABA (inhibitory) afferent: parallel fiber, mossy fiber rosette efferent: granule cell dendrite 23 Micro-circuitry of the cerebellum 24 12
13 Micro-circuitry of the cerebellum 25 Micro-circuitry of the cerebellum Cerebellar overview Parallel fiber Purkinje Cell Granule cell GABA inhibitory Mossy Fiber Pontine nuclei from Brain stem 26 13
14 Micro-circuitry of the cerebellum Parallel fiber Stimulus -response loop Purkinje Cell Granule cell Pontine nucleus mossy fiber cbll cuclei motor system Mossy Fiber Motor system Pontine nuclei from brain setm 27 Purkinje Cell Micro-circuitry of the cerebellum Parallel fiber Granule cell Not broken Don t fix it Feed-forward inhibition inhibits stimulusresponse loop GABA inhibitory Mossy Fiber Pontine nuclei from Brain stem 28 14
15 Purkinje Cell Micro-circuitry of the cerebellum Parallel fiber Olive disinhibts stimulusresponse loop Climbing fiber Granule cell Mossy Fiber Motor system Olive cell Pontine nuclei from Brain stem 29 Purkinje Cell Micro-circuitry of the cerebellum Parallel fiber Expected events inhibit the olive Climbing fiber Granule cell Mossy Fiber Motor system Olive cell - Pontine nuclei from Brain stem 30 15
16 Micro-circuitry of the cerebellum Purkinje Cell Parallel fiber Unexpected events become expected events Climbing fiber Granule cell GABA inhibitory Mossy Fiber Motor system Olive cell - Pontine nuclei from Brain stem 31 Micro-circuitry of the cerebellum Cerebellar basic circuit Pontine inputs attempt to evoke motor response: pons to cerebellar nuclei to motor systems Stimulus-response loop Feedforward inhibition blocks the stimulus-response loop: mossy fibers excite granule cells parallel fibers excite Purkinje cells Purkinje cells inhibit cerebellar nuclei Unexpected events disconnect feedforward inhibition: Olive via climbing fibers to Purkinje cells Synapses from parallel fibers depressed(ltd) Stimulus-response loop is disinhibited: Pons to cerebellar nuclei to motor systems Newly expected events inhibits olive: Cerebellar nuclei inhibit olive(gaba) 32 16
17 Micro-circuitry of the cerebellum Long Term Depression Climbing fiber from olive Parallel fiber from granule cell Purkinje Cell Ca 2+ Purkinje cell inhibits cerebellar nuclei Na + Before learning 33 Micro-circuitry of the cerebellum Long Term Depression Climbing fiber from olive Parallel fiber from granule cell Purkinje Cell Ca 2+ Kinase Phosphorylation Uncxpected event 34 17
18 Micro-circuitry of the cerebellum Long Term Depression Climbing fiber from olive Parallel fiber from granule cell Purkinje Cell Purkinje cell unable to inhibit cerebellar nuclei Long Term Depression Next occasion 35 Micro-circuitry of the cerebellum Long Term Depression 36 18
19 Micro-circuitry of the cerebellum Long Term Depression Model suggested by Marr and Albus (1970s) The climbing fiber weakens the parallel fiber Purkinje cell synapse in a process called long-term depression (LTD). (Masao Ito, 1980s) pf active no LTD pf & cf both active repeatedly LTD (associative plasticity) The climbing fiber compares what is intended with what has happened and provides an error signal that would depress the parallel fibers that are active concurrently and allow correct movement to occur. 37 Cerebellum and motor learning in gait Cortex : vermis Nucleus : fastigial Medial cerebellar system modulates ventromedial systems for extension of multiple proximal joints Cortex : flocculus nodule(of vermis) Nucleus : vestibular Medial cerebellar systems 38 19
20 Cerebellum and motor learning in gait Pontine reticulospinal : anatomy 39 Cerebellum and motor learning in gait Lateral vestibulospinal : anatomy 40 20
21 Cerebellum and motor learning in gait VMS The olive balances excitation against inhibition 41 Cerebellum and motor learning in gait Lateral cerebellar system modulates dorsolateral systems for flexion of single distal joints Cortex : paravermis Nucleus : globose & emboliform Cortex : hemispheres Nucleus : dentate Lateral cerebellar systems 42 21
22 Cerebellum and motor learning in gait Rubrospinal system 43 Cerebellum and motor learning in gait Corticospinal system 44 22
23 Cerebellum and motor learning in gait Hyperflexion DLS Hypoflexion The olive balances excitation against inhibition 45 Cerebellum and motor learning in gait Cerebellar nuclei excite motor systems Cerebellar cortex inhibits the excitation CC DCN MS Cortex active 46 23
24 Cerebellum and motor learning in gait The olive responds to unexpected events & disconnects the inhibition ION And no more unexpected Events occur CC DCN MS Olive active 47 Cerebellum and motor learning in gait Until extension across multiple proximal joints is balanced against flexion across single distal joints Olive active 48 24
25 Cerebellum and motor learning in gait Alternation of side and phase 49 Cerebellum and motor learning in gait Alternation of side and phase 50 25
26 Cerebellum and motor learning Cerebellar systems 51 Cerebellum and motor learning GABA a GABA b receptors: Chloride channels open 10ms route receptors: calcium channels close 300ms repetition Pre-synaptic inhibition 52 26
27 Cerebellum and motor learning Vestibulo-ocular reflex 53 Cerebellum and motor learning 1. Turn head 2. Eyes in the wrong direction 3. Vestibular nucleus over-correction 4. Cerebellar feed forward-inhibition over correction 5. Retina-pretecto N. olive in the midbrain projection fine tunes to see exactly Correction of over-correction of over-correction! 54 27
28 Cerebellum and motor learning Olivary nucleus Unconditioned stimulus Cerebellar cortex Interpositus nucleus Red nucleus Pontine nuclei Conditioned stimulus Facial nucleus Response Classical conditioning : pair CS and UCS 55 Memory stored here Cerebellum and motor learning Cerebellar cortex Pontine nuclei Interpositus nucleus Conditioned stimulus Red nucleus Facial nucleus Response Classical conditioning : conditioned response 56 28
29 Neocerebellar cortex Dentate n. Mossy fibers Association cortex Pontine n. Basal ganglia Thalamus (VLp) Motor cortex Supplementary & premotor cortex Novice Spinal cord 57 Neocerebellar cortex Dentate n. Mossy fibers Association cortex Pontine n. Basal ganglia Thalamus (VLp) Olive Red n. Motor cortex Supplementary & premotor cortex Spinal cord Olive disinhibits 58 29
30 Association cortex Pontine n. Basal ganglia Dentate n. Olive Red n. Thalamus (VLa) Thalamus (VLp) Motor cortex Supplementary & premotor cortex Spinal cord Dentate path opens 59 Association cortex Dentate n. Thalamus (VLa) Motor cortex Pontine n. Basal ganglia Thalamus (VLp) Supplementary & premotor cortex Spinal cord Plasticity 60 30
31 Neocerebellar cortex Association cortex Pontine n. Basal ganglia Dentate n. Thalamus (VLp) Motor cortex Supplementary & premotor cortex Spinal cord Skilled 61 Examples of cerebellar learning Modification of spinal reflexes: Presynaptic re-routing of stretch reflex Modification of central pattern generators: Amplitude of flexion & extension in swing &stance Modification of vestibular reflexes: Amplitude of vestibulo-ocular reflexes Acquisition of conditioned reflexes: Conditioned eye-blink Acquisition of skilled motor patterns: Cortico-ponto-cerebellar loops 62 31
32 REFERENCE Motor contorl in the human movement(ppt), by Dr. Nigel Lawes(Int. seminar in Aug, 2006) Cerebellum(Current funtional concept)(ppt) by 문승국 (Bobath 학술대회, Nov, 2006) Neuroscience exploring the brain 2 nd edition by Mark. F bear etc., Lippincott Williams & Wilkins The neuroscience of human movement by Charles T. Leonard, Mosby Motor Control 2 nd edition by Amne Shumway-cook&Marjorie H. Woollacott, Lippincott Williams & Wilkins Neuroscience 2 nd (Fundamentals for rehabilitation) by Laurie Lundy-Ekman, Saunders Neurology and neurosurgery illustrated 4 th edition by Kenneth W. Lindsay & Ian bone, Churchill Livingstone Principles of Neural Science 4 th edition by EricR. Kandel etc, Mcgrawhill 63 Thank you!! Have a nice weekend!! Let s go skiing 64 32
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