1. Cerebellum and movement modulation
Domina Petric, MD

2. Cerebellar function overview
Error correction and motor learning:
cerebellum integrates executive commands with sensory feedback for movement-to-movement adjustment of behavior
facilitates learning when errors are numerous
outputs are directed toward circuits of upper motor neurons

3. Cerebellar function overview
Cerebellum is an organ of agility:
coordination of ongoing, multi-jointed movement
coordination of ongoing, multi-jointed cognitive processes (for example, problem solving)

4. Major parts of the cerebellum
Cerebellar cortex
Deep nuclei of the cerebellum
Cerebellar peduncles:
MIDDLE is the largest one and drives signals from the brainstem and pons INTO the cerebellum
SUPERIOR drives signals OUT OF the cerebellum
INFERIOR is BIDIRECTIONAL (inputs from the spinal cord into the cerebellum and efferent signals from the cerebellum)

5. Functional subdivisions of the cerebellum:
Spinocerebellum includes a medial strip of the cerebellar cortex: the central part is the VERMIS.
Cerebrocerebellum comprises most of the cerebellum (lateral cerebellar hemispheres): skilled movements of the distal extremities.
Vestibulocerebellum: flocculus and nodulus (flocculo-nodular lobe) and it is connected with vestibular nuclei.

6. Functional subdivisions of the cerebellum

7. Contains the body map which is fractionated:
Spinocerebellum
Contains the body map which is fractionated:
axial representation is in the vermis
representation of the distal extremities extends outward from the vermis into the paramedian strip of the cerebellar cortex

8. Cerebellar cortex and deep nuclei
Cerebellar cortex has folia (like gyri in cerebral cortex).
Deep cerebellar nuclei are fastigial nucleus, interposed nuclei and dentate nucleus.

9. Deep cerebellar nuclei
Dentate nucleus
Fastigial nucleus
Interposed nuclei

10. Inputs to the cerebellum
Inputs to the cerebellum come from the pontine nuclei, inferior olive, spinal cord and vestibular nuclei.
Inputs from PONTINE NUCLEI project to the contralateral cerebellar hemisphere via the middle cerebellar peduncle.
Pontine nuclei recieve inputs from frontal and parietal cortex.
Inputs from INFERIOR OLIVE project to the contralateral cerebellar hemisphere via the inferior cerebellar peduncle: LEARNING SIGNAL.
The inferior olive recieves inputs from the RED NUCLEUS and those inputs are from frontal and parietal cortex.

11. Inputs to the cerebellum
Midline
Frontal and parietal cerebral cortex
RED NUCLEUS
PONTINE NUCLEI
Middle cerebellar peduncle
Cerebellar cortex and deep nuclei
VESTIBULAR NUCLEI
SPINAL CORD
Inferior cerebellar peduncle
INFERIOR OLIVE

12. Afferent fibers
Mossy fibers: most of afferent inputs to the cerebellum.
Climbing fibers: afferent inputs from the inferior olive to the cerebellum.
Both mossy fibers and climbing fibers end up in the cerebellar cortex and deep cerebellar nuclei.
Dorsal spinocerebellar tract is the major relay of proprioceptive signals from the lower extremities into the cerebellum and it is IPSILATERAL.
Cuneocerebellar tract is the major relay of proprioceptive signals from the upper extremities into the cerebellum (ipsilateral).

13. Afferent fibers
Signals from spinal cord end up in the SPINOCEREBELLUM.
Afferent inputs from PONTINE NUCLEI end up in the lateral cerebellar hemispheres: CEREBROCEREBELLUM.
Afferent inputs from VESTIBULAR NUCLEI end up in VESTIBULOCEREBELLUM.

14. IPSILATERAL REPRESENTATION PRINCIPLE
Cerebellum is representing the IPSILATERAL side of the body.
Cerebral cortex is representing the CONTRALATERAL side of the body.

15. Cerebellar cortex
PURINJE CELL is the principal neuron in the cerebellar cortex.
Granule cells have a long axon that splits into two parts: PARALLEL FIBERS.
Granule cells are getting excitatory input from MOSSY FIBERS and then send excitatory input to the Purkinje cells.
The Purkinje cells send their axons down through the white matter where they synapse on cells in the deep cerebellar nuclei: inhibitory synapse.
Purkinje cells release GABA!

16. Cerebellar cortex
The climbing fiber is derived from the inferior olivary nucleus.
The climbing fiber makes contact with single Purkinje cell and wraps its axons around the proximal dendrites of Purkinje cell.
This is one of the most powerfull synapses in the human brain.
Climbing fiber also gives excitatory input directly to the deep cerebellar nuclei.
There is DEEP EXCITATORY LOOP for the deep cerebellar nuclei and CORTICAL INHIBITORY LOOP that modulates the action of the deep cerebellar nuclei.

17. Motor learning
Motor learning is consistent with a stronger output from the cerebellum.

18. Calcium
High levels of calcium in the cerebral cortex lead to long term potentiation.
High levels of calcium in the CEREBELLAR CORTEX lead to LONG TERM DEPRESSION.

19. Ascending outputs from the cerebellum
Outputs from the deep cerebellar nuclei (dentate nucleus and interposed nuclei) travel via the SUPERIOR CEREBELLAR PEDUNCLE into the VL COMPLEX OF THE THALAMUS and SUPERIOR COLLICULUS.
Ascending axons from the cerebellum CROSS THE MIDLINE to provide outputs to the contralateral cerebral hemisphere.
Red nucleus recieves collaterals from ascending axons.
Thalamus sends signals to the primary motor cortex and premotor cortex.

20. Descending outputs from the cerebellum
Major descending output is from the fastigial cerebellar nucleus to the RETICULAR FORMATION.
Reticular formation sends signals to the lower motor neurons in medial ventral horn.
Fastigial nucleus is also connected to SUPERIOR COLLICULUS.
VESTIBULAR NUCLEI recieve direct input from the Purkinje cells like they are deep cerebellar nuclei displaced from the cerebellum.
Vestibular nuclei send signals to the lower motor neurons in medial ventral horn: POSTURE and BALANCE.

21. Cerebellar organisation overview
Cerebrocerebellum
Spinocerebellum
Vestibulocerebellum
Dentate nucleus
Interposed nuclei, fastigial nucleus
Vestibular nuclei
Premotor cortex: motor planning
Motor cortex and brainstem: motor execution
Lower motor neurons in spinal cord and brainstem: balance and vestibulo-ocular regulation

22. Cerebellar dysfunction
Clinical (motor) signs of cerebellar lesions are always ipsilateral to the lesion because cerebellum represents ipsilateral body and spinocerebellar pathways are ipsilateral.
ATAXIA: incoordination of movement.
INTENTIONAL TREMOR: tremor during movement.
DYSMETRIA: instability of a limb as it approaches a target, overshooting or undershooting.
IMPAIRMENT of rapid, repetitive movements.
DECOMPOSITION of movements.

23. Cerebellar dysfunction in alcoholism
There is degeneration of ANTERIOR PART OF THE VERMIS.
ALCHOHOLIC CEREBELLAR ATROPHY!

24. Literature
Leonard E. White, PhD, Duke University