The Cerebellum Lu Chen, Ph.D. MCB, UC Berkeley 1 Outline Overview Structure Micro-circuitry of the cerebellum The cerebellum and motor learning 2
Overview Little brain 10% of the total volume of the brain, more than 50% of neurons of the entire brain Structural regularity Control fine movement coordination, balance and muscle tone. Influences the motor systems by evaluating the disparities between intention and action. Adjusts the operation of motor centers in the cortex and the brain stem while a movement is in progress. 3 The relationship of the cerebellum to the cortical motor area Premotor area Supplementary motor cortex Primary motor cortex Cerebral Cortex Thalamus Cerebellar Thalamus cortex Relay nuclei Cerebellum 4
Three aspects of organization 1. Input: from brain stem and cortex, extensive information about the goals, commands, and feedback signals associated with the programming and execution of movement. 2. Output: motor and premotor systems of the cortex and brain stem. 3. Synaptic plasticity supports motor adaptation and learning. 5 Structure of the Cerebellum 6
Structure of the Cerebellum Dorsal View Cortex: vermis Hemisphere: intermediate lobe lateral lobe Deep nuclei: Dentate nucleus Cerebellar peduncles Interposed nuclei Fastigial nucleus flocculonodular lobe 7 Structure of the Cerebellum Midsagittal View Midbrain Pons Folium Brain stem Medulla 8
Overview of cerebellar control of movement Vestibular afferents Head and proximal body (visual, auditory, vestibular) Flocculonodular lobe Vermis Lateral vestibular nuclei Fastigial nucleus Balance and eye movement Brain stem (medial descending system) Posture, gaze 9 Overview of cerebellar control of movement limbs (somatosensory) Cerebral cortex Intermediate hemisphere Lateral hemisphere Interposed nucleus Dentate nucleus Corticospinal and rubrospinal systems (lateral descending system) Motor, premotor and prefrontal cortices Limbs and digits movement Planning and mental rehearsal of complex movement 10
Common Symptoms Related to Cerebellar Lesions Hypotonia a diminished resistance to passive limb displacement Ataxia lack of coordination Intention tremors during movement 11 Structure of the Cerebellar Cortex surface Stellate cell Molecular layer Basket cell Purkinje cell layer Purkinje cell Golgi cell Granule cell glomerulus Granule cell layer Climbing fiber Mossy fiber 12
Micro-Circuitry of the Cerebellum Input to the cerebellum: mossy fiber and climbing fiber, both are excitatory (glutamate) Output from the cerebellar cortex: Purkinje cell axon, inhibitory (GABA) Output from the cerebellum: cerebellar deep nuclei, excitatory 13 Micro-Circuitry of the Cerebellum Purkinje cell 2-dimensional dendritic tree The only output of the cerebellar cortex Receives input from climbing fiber and parallel fiber (granule cell axon) Granule cell Small, large quantity Input: mossy fiber Output: parallel fiber to Purkinje cells 14
Two excitatory pathways in the cerebellar cortex 1 Mossy fiber Granule cells Parallel fiber Purkinje cells output Climbing fiber 2 1: one parallel fiber thousands of Purkinje cells one Purkinje cell 200,000 parallel fiber Simple spike in Purkinje cell evoked by mossy fiber input 2: one climbing fiber 1-10 Purkinje cells one Purkinje cell one climbing fiber, many synapses complex spikes in Purkinje cell 15 Local inhibitory pathways in the cerebellar cortex Lateral inhibition by Stellate cell and basket cell, - Parallel fiber Stellate, basket Purkinje cell Golgi cell: inhibit granule cells, negative feedback - Parallel fiber Golgi cell granule cell 16
Micro-circuitry of the cerebellum Cerebellar cortex pf Golgi cell - Granule cell Stellate/ Basket Purkinje cell - - Deep nuclei Climbing fiber Mossy fiber Output of the cerebellum 17 The cerebellum and motor learning 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. 18
The cerebellum and motor learning 19 The cerebellum and motor learning 20