3: Cerebellum

Question 1

(OBJ) Describe the relationship of the cerebellum to the brainstem, and explain how information travels in and out of the cerebellum.

Answer 1

CEREBELLAR PEDUNCLES: tracts of white matter that join cerebellum to brainstem

• -Superior CP: cerebellum -> decussate -> midbrain [-> VL/VA of thalamus or red nucleus] (output)
• -Middle CP (aka brachium pontis): cerebral cortex -> pons -> cerebellum (input)
• -Inferior CP: medulla + spinal cord cerebellum (input and output)

Question 2

(OBJ) Define the anatomical (5) subdivisions of the cerebellum.

Answer 2

Two hemispheres connected in midline by vermis
Folia = transverse folds; a core of white matter within a thin layer of cortex
–Arbor vitae = white matter looks like tree in sagittal view
Primary fissure = separates anterior and posterior lobes
Posterolateral fissure = separates posterior and flocculonodular lobes
Tonsil = lobule superior to the foramen magnum

Question 3

(OBJ) Explain the cellular organization of the cerebellar cortex. Briefly summarize synaptic interactions.

Answer 3

(from surface in)
MOLECULAR LAYER: contains dendrites of Purkinje cells and axons/parallel fibers from granule cells
PURKINJE LAYER: single layer of large Purkinje cells
GRANULE CELL LAYER: contains huge numbers of tiny granule cells and their dendrites, axons of Purkinje cells, mossy fibers, & climbing fibers

Mossy fibers -!-> granule cells -!-> Purkinje cells
Climbing fibers -!!!-> Purkinje cells

Question 4

List and give the function of the three functional subdivisions of the cerebellum.

Answer 4

Vestibulocerebellum: flocculonodular lobes
–Regulates vestibular activity, coordinates reflex eye movements

Spinocerebellum: vermis, intermediate zone of cerebellum
–Regulation of muscle tone, monitoring of execution of movement; corrects for motor error or changing circumstances of the body

Cerebrocerebellum: lateral hemispheres
–Planning, learning, and initiating complex (highly skilled) voluntary motor sequences

Question 5

Briefly state the primary function of the cerebellum. How does it perform this function? Generally, what happens when it is damaged?

Answer 5

Modulate movement: detect motor error and provide corrections to improve performance
–Controls IPSILATERAL side of body
Acts by regulating the activity of upper motor neurons in the descending motor pathways
Damage -> clumsy and uncoordinated movement

Question 6

Explain the significance of the cerebellar tonsil.

Answer 6

In situations of increased pressure, may herniate down through foramen magnum and compress respiratory centers in medulla and spinal cord

Question 7

Why does alcohol have such a severe effect on the cerebellum?

Answer 7

All five types of cerebellar neurons (except granule cells) use GABA as their neurotransmitter (all are inhibitory)

Question 8

(mOBJ) What are the five cell types of the cerebellum? What layer is each in?

Answer 8

*Purkinje cells - Purkinje layer
*Granule cells - granular layer
Golgi cells (few) - granular layer
Basket cells - molecular layer
Stellate cells - molecular layer

Question 9

(mOBJ) Describe Purkinje cells.

Answer 9

The ONLY output from the cerebellar cortex
Cell body in Purkinje layer
Dendrites extend into molecular layer and branch extensively at right angles
Axon extends into white matter -> deep cerebellar nuclei or vestibular nucleus

Question 10

(mOBJ) Describe granule cells.

Answer 10

Most abundant type of neuron in brain
Soma and dendrites located in granular layer
Axon -> molecular layer, then divides and spreads -> excitatory synapse on Purkinje cells
–Axons = “parallel fibers”
–TONS of parallel fibers synapse on each Purkinje cell

Question 11

(mOBJ) Describe mossy fibers.

Answer 11

Name for the terminations of axons coming from other parts of the brain (spinocerebellar tracts, pontocerebellar tracts, etc)
Primary source of input to Purkinje cells
Synapse on granule cells in granular layer -!-> granule cells -!-> parallel fibers -!-> Purkinje cells

Question 12

(mOBJ) Describe climbing fibers.

Answer 12

Direct source of powerfully EXCITATORY input to Purkinje cells from inferior olive
–Highly specific: one olivary neuron -> one or two Purkinje cells
Axon extends from inferior olivary nucleus -> inferior cerebellar peduncle -> Purkinje cell and wraps around it

Question 13

Name the three deep cerebellar nuclei and from where each receives input. What is their significance? Which is the largest?

Answer 13

Fastigial nucleus (medial): input from Purkinje cells of vermis
Interposed nuclei (globose & emboliform): input from intermediate zone
Dentate nucleus (lateral): LARGEST, input from lateral hemispheres, output -> superior cerebellar peduncle -> decussates

Significance: most cerebellar output is integrated in the deep cerebellar nuclei before it leaves the cerebellum

Question 14

Give a general overview of cerebellar circuits

Answer 14

Excitatory input from inferior olive -> climbing fibers -!!!-> Purkinje cells
Excitatory input from rest of brain -> mossy fibers -!-> granule cells + parallel fibers -!-> Purkinje cells
–Climbing fibers & mossy fibers -!-> deep cerebellar nucleus neurons via collaterals on their way up
Activated Purkinje cells -x-> deep cerebellar nuclei

Question 15

What is inhibitory sculpting?

Answer 15

The manner in which excitatory output from the deep cerebellar nuclei is modified by inhibitory output of the Purkinje cells from the cerebellar cortex

Question 16

How is the cerebellum involved in learning? (maybe delete?)

Answer 16

SYNAPTIC PLASTICITY between parallel fibers and Purkinje cells
Changes -> short-term error correction & long-term motor learning

Question 17

Define motor learning.

Answer 17

Improvements in motor performance due to practice of motor skills

Question 18

Differentiate between short-term synaptic plasticity and long-term synaptic plasticity.

Answer 18

Short-term: changes lasting a few minutes or less; occur due to some form of local inhibition
Long-term: changes lasting >30 minutes; involve up- or down-regulation of synthesis and trafficking of receptors

Question 19

Briefly describe the synapse between climbing fibers and Purkinje cells: what neurotransmitter is used? When are climbing fibers activated? What happens in the Purkinje cell upon synaptic transmission?

Answer 19

NT = aspartate
Activated in the case of MOTOR ERROR (motor performance =/= expectation)
Powerfully excites Purkinje cell & opens Ca channels

Question 20

Describe the synapse between parallel fibers and Purkinje cells: what neurotransmitter is used? How does synaptic depression occur? (overview, 6 steps)

Answer 20

NT = glutamate -> AMPA/metabotropic glutamate receptors

Every parallel fiber to Purkinje cell synapse active at the same time as the arrival of the error signal from the climbing fiber will be weakened for future inputs

1. Climbing fiber activation -> Ca influx into Purkinje dendrite
2. Parallel fiber activation -> metabotropic glu receptor activation -> IP3 release
3. IP3 + Ca -!-> PKC
4. PKC phosphorylates AMPA receptors
5. Phosphorylated AMPA receptors have decreased effficacy and greater likelihood of internalization
6. Result = decreased response to future activation

Question 21

(OBJ) Vestibulocerebellum: sources of input, targets of output, the specific peduncles through which information travels, and the tracts that are affected by the output.

Answer 21

Vestibulocerebellum: flocculonodular lobes

• -INPUT from vestibular apparatus (internal ear) and vestibular nuclei (brainstem)
• -OUTPUT: projects ipsilaterally to vestibular nuclei
• -PEDUNCLE: inferior cerebellar peduncle [input and output]
• -TRACTS: vestibulospinal tract (regulation of postural movements to maintain body equilibrium and muscle tone), extraocular nuclei (regulates vestibulo-ocular reflex)

Question 22

(OBJ) Spinocerebellum [vermis]: sources of input, targets of output, the specific peduncles through which information travels, and the tracts that are affected by the output.

Answer 22

Spinocerebellum: vermis, intermediate zone of cerebellum

• -INPUT from spinocerebellar pathways (proprioceptive information about ipsilateral side of body); also visual and auditory input
• -OUTPUT: vermis -> ipsilateral fastigial nucleus -> bilaterally to brainstem (vestibular nuclei, reticular formation)
• -PEDUNCLE: inferior peduncle [input, output]
• -TRACTS: fastigial nucleus -(bilateral)-> Vestibulospinal & reticulospinal tracts (axial muscle function); ventral corticospinal tract (axial muscle function); corticobulbar tracts (facial/tongue muscle function)

Question 23

(OBJ) Spinocerebellum [intermediate zone]: sources of input, targets of output, the specific peduncles through which information travels, and the tracts that are affected by the output.

Answer 23

Spinocerebellum: vermis, intermediate zone of cerebellum

• -INPUT from spinocerebellar pathways (proprioceptive information about ipsilateral side of body); also visual and auditory input
• -OUTPUT: intermediate zone -> ipsilateral interposed nuclei -> contralateral red nucleus & motor cortex via VL
• -PEDUNCLE: inferior peduncle [input], superior cerebellar peduncle [output]
• -TRACTS: interposed nucleus -(contralateral)-> rubrospinal tract & lateral corticospinal tracts (also decussate -> ipsilateral limb muscles)

Question 24

Characterize the somatotopy of the spinocerebellum: where are trunk muscles represented? Limb muscles?

Answer 24

Trunk muscles in VERMIS

Limb muscles in INTERMEDIATE ZONE

Question 25

(OBJ) Cerebrocerebellum: sources of input, targets of output, the specific peduncles through which information travels, and the tracts that are affected by the output.

Answer 25

Cerebrocerebellum: lateral hemispheres

• -INPUT: broad areas of cerebral cortex -> pontine nucleus (corticopontine tract) -> transverse pontine fibers (decussate)
• —>Tells cerebellum what cortex is doing or planning to do
• -OUTPUT: ipsilateral dentate nucleus -(decussate)-> VL of thalamus & red nucleus
• -PEDUNCLE: middle cerebellar peduncle [input], superior cerebellar peduncle [output]
• -TRACTS:
• –>Dentothalamic fibers -> VL of thalamus -> motor & premotor cortices -> corticospinal & corticobulbar tracts (affect contralateral motor output -(decussate)-> affect ipsilateral motor FUNCTION)
• –>Dentatorubral fibers -> red nucleus -> inferior olive -(decussate)-> inferior cerebellar peduncle -> CLIMBING FIBERS! (affect ipsilateral Purkinje cell activity via error detection; critical for motor learning)

Question 26

What is the triangle of Molleret? What results from interference with this system?

Answer 26

Cerebrocerebellum -(decussation)-> red nucleus -> inferior olive -(decussation)-> cerebellar Purkinje cells

Interference = severe incoordination

Question 27

(OBJ) Discuss the deficits associated with cerebellar lesions.

Answer 27

(done previously)

Question 28

Which systems send afferent projections to the cerebellum through the inferior cerebellar peduncle?

Answer 28

Vestibular
Vast majority of spinal
Reticular formation
Inferior olive (climbing fibers)

Question 29

Which systems send afferent projections to the cerebellum through the middle cerebellar peduncle?

Answer 29

Pontine nuclei (relay from cortex and tectum)
--Corticopontine-pontocerebellar pathway is the largest input