Modulation of Movement by the Cerebellum

Question 1

How does the cerebellum influence movement?

Answer 1

The efferent cells of the cerebellum do not project directly to the local circuits of the brainstem and spinal cord, instead the cerebellum influences movement primarily by modifying the activity patterns of the upper motor neurons

Question 2

Describe the anatomy of the cerebellum

Answer 2

The cerebellum has two main grey matter structures
1. Laminated cortex on its surface
2. Clusters of cells in nuclei buried deep in the white matter of the cerebellum

Question 3

What is a primary function of the cerebellum?

Answer 3

Muscle control including balance and movement

To detect the difference or ‘motor error’ between an intended movement and the actual movement, and through its influence over upper motor neurons, to reduce the error

Question 4

How can the cerebellar hemispheres be subdivided?

Answer 4

Into 3 main parts based on differences in their sources of input
1. Cerebrocerebellum - occupies most of the lateral part of the cerebellar hemisphere and receives input, indirectly, from many areas of the cerebral cortex - involved with the regulation of highly skilled movements, especially planning and execution of complex spatial and temporal sequences of movement
2. Spinocerebellum - occupies the median and paramedian zones of the cerebellar hemispheres and is the only part that receives input directly from the spinal cord
3. Vestibulocerebellum - includes the flocculus and nodulus, receives input from the vestibular nuclei in the brainstem and is concerned primarily with the vestibulo-ocular reflex and with the regulation of movements that maintain posture and equilibrium

Question 5

What are the layers of the cerebellum?

Answer 5

Molecular layer = parallel fibres, basket cells, stellate cells, Purkinje cells dendrites

Purkinje cell layer = Purkinje cells and climbing fibres

Granular layer = granule cells, golgi cells, mossy fibres

Question 6

What nuclei are found in each of the 3 subdivisions of the cerebellum?

Answer 6

Cerebrocerebellum = dentate nucleus
Spinocerebellum = Interposed nuclei
Vestibulocerebellum = Fastigial nucleus

Question 7

Where does the entire cerebellum receive modulatory input from?

Answer 7

The inferior olivary nucleus (medulla) - involved in learning and memory functions served by cerebellar circuitry

Question 8

Describe the relevance of mossy fibres in the cerebellum

Answer 8

Major input source to the cerebellum
Part of the white matter underlying the cortex and synapse onto granule cells in the granular layer

Question 9

Describe the relevance of granule cells in the cerebellum

Answer 9

Cerebellar granule cells are the most numerous neurons of the brain - outnumber mossy fibres by at least 50 to 1
Send their axons to the molecular layer, where they are split into 2 to create parallel fibres
These form synapses with the Purkinje cells

Question 10

Describe the relevance of Purkinje cells in the cerebellum

Answer 10

Cell bodies in the middle of the Purkinje cell layer
Sole output cells of the cerebellar cortex
Each Purkinje cell layer receives approx 150,000 parallel fibre synapses

Question 11

What are the major pathways of the cerebellum?

Answer 11

Cerebellar peduncles
1. Superior cerebellar peduncle = efferent
deep cerebellar nuclei - motor nuclei of thalamus - upper motor neurons in cerebral cortex

2. Middle cerebellar peduncle = afferent
   - pontine nuclei
3. Inferior cerebellar peduncle = afferent and efferent
   afferent = vestibular nuclei and spinal cord
   efferent = vestibular nuclei and reticular formation

Question 12

Describe the largest afferent pathway within the cerebellum

Answer 12

Vestibulocerebellar pathway
Arises in the widespread areas of the cerebral cortex and terminates in the pontine nuclei of the basal pons, which in turn project to the contralateral cerebellum (through mossy fibres)

The axons from the pontine nuclei are the mossy fibres which send collateral branches that synapse both on neurons in the deep cerebellar nuclei and on granule cells in the granule cell layer of the cerebellar cortex

Cerebellar granule cells give rise to axons called parallel fibres that ascend to the outermost molecular layer of the cerebellar cortex

The parallel fibres bifurcate in the molecular layer to form T-shaped branches that extend for several millimetres parallel to the orientation of the small cerebellar gyri. There they form excitatory synapses with the dendritic spines of the underlying Purkinje cells

Question 13

Describe the relevance of climbing fibres

Answer 13

Each Purkinje cell receives input from a single climbing fibre
Climbing fibres are the axons of cells in the inferior olive, at the base of the brain stem
Climbing fibres wrap themselves around Purkinje cell dendritic trees forming at least 1000 synapses

Question 14

What inputs moderate the inhibitory activity of Purkinje cells?

Answer 14

GABAergic interneurons
Basket cells (inhibitory nests of synapses made with Purkinje cell bodies)
Stellate cells (receives input from the parallel fibres and provides an inhibitory input to the Purkinje cell dendrites)

Question 15

What do Golgi cells do?

Answer 15

Apical dendrites of inhibitory interneurons found in the molecular layer
Cell bodies in the granular cell layer
Receive input from the parallel fibres and provide an inhibitory feedback to the cells of origin of the parallel fibres

Question 16

What does the parallel fibre input to the Purkinje cells give rise to?

Answer 16

Give rise to individual and spontaneous action potentials called simple spikes that typically fire at a much higher rate (30 to 100 Hz)

Question 17

What does the activation of climbing fibres induce in Purkinje cells?

Answer 17

A strong excitatory postsynaptic potential in Purkinje cells that generates an initial action potential followed by series of smaller spikes - this postsynaptic response is termed a complex spike

Very reliable - whenever climbing fibre fires, Purkinje cell fires

Low frequency of firing compared to simple spikes, so little effect on output

Question 18

What is involved in accurate movements?

Answer 18

For animals and humans learning appears to be involved
As adults we make accurate movements ‘naturally’ but babies spend a lot of their time learning about movements
Cerebellar damage typically does not produce paralysis - other parts of the brain issue movement commands and carry them out inaccurately; the role of the cerebellum is to ensure they are carried out properly

Question 19

What did Brindley (1964) suggest?

Answer 19

The purpose of the cerebellum is to learn motor skills, so that when they have been learned a simple or incomplete message from the cerebrum will suffice to provoke execution

Question 20

What is the Marr-Albus Framework?

Answer 20

Key idea = to learn to make accurate movements you must have information about what you did wrong - ‘an error signal’
Climbing fibres convey that error signal

Question 21

What is the suggested learning rule in the Marr Albus framework?

Answer 21

A synaptic weight (between parallel fibre and Purkinje cell) is changed according to the correlation between the parallel fibres signal and the error signal conveyed by the climbing fibre

–> If there is a positive correlation, reduce the weight
–> If there is a negative correlation, increase the weight

Learning stops when there is no longer a correlation between any parallel fibre signal and the climbing fibre signal

Can therefore be called a decorrelation learning rule

Question 22

What evidence is there for decorrelation learning rule?

Answer 22

Evidence in favour of this idea = long-term depression
–> Pair stimulation of parallel fibres with stimulation of climbing fibres
Synapses between parallel fibres and Purkinje cell become depressed
Consistent with ‘error signal’ idea: parallel fibre signals positively correlated with climbing fibre signals

Question 23

Explain the signalling that occurs at parallel fibre synapses during long term synaptic depression

Answer 23

Glutamate released by parallel fibres activates both AMPA-type and metabotropic receptors
Metabotropic receptors produce IP3 and DAG in the Purkinje cell
When paired with a rise in Ca2+ associated with activity of climbing fibre synapses, the IP3 causes Ca2+ to be released from the endoplasmic reticulum, while Ca2+ and DAG together activate protein kinase C
These signals together change the properties of AMPA receptors to produce long term depression

Question 24

What reflex has been used to test if this theory of the cerebellum works?

Answer 24

Vestibulo-ocular reflex
- If the retinal image moves visual processing is degraded - some kinds of visual information are lost
-If the eyes stay still then image movement would be produced by e.g., the head movements that occur during walking
-Consequently, the eyes counter-rotate with the head to exactly offset the head movement - this is the vestibulo-ocular reflex

Question 25

How has the VOR provided evidence of cerebellar learning in movement?

Answer 25

There needs to be constant maintenance e.g., learning so that the VOR knows how big an eye movement command to send to the eye muscles
Tested with monkeys wearing magnifying or minifying spectacles
As the glasses alter the size of the visual image on the retina, the compensatory eye movements, which normally would maintain a stable image of an object on the retina, are either too large or too small
Over time, individuals learn to adjust the distance the eyes must move in response to head movements to accord with the artificially altered size of the visual field

Question 26

What region of the cerebellum has been implicated in the VOR?

Answer 26

The flocculus
Inactivation of this region prevents VOR adaptation

Question 27

What is the circuit in the VOR?

Answer 27

The flocculus is located on a side-path to the main reflex

Semi-circular canals (liquid-filled tubes in the ear) send signals to the brainstem
Eye movement command sent to the eye muscles
Copy of eye movement command is sent to the flocculus which sends signals back to the semi-circular canals

Question 28

What are the floccular inputs into the VOR circuit?

Answer 28

Mossy fibre inputs = convey information about eye movement commands
Climbing fibre inputs = convey information about retinal image movement

Question 29

How is the VOR controlled by cerebellar learning?

Answer 29

If gaze-holding fails, there is a retinal slip, which therefore corresponds to an error signal with respect to gaze-holding
If there is no correlation between motor commands and the error, then there is no causation; any observed retinal slip must be due to external factors and not to inaccurate motor commands
Conversely, if there is a correlation between motor command and retinal slip error, then the motor commands are incorrect
The correlation between efference copy and retinal slip is therefore an important source of information about the accuracy of motor commands

Question 30

What else is the cerebellum involved in?

Answer 30

Historically, the main effects of cerebellar damage were on movements
But now cerebellum thought to be involved in much more
- Sensory prediction
- Active sensing
- Emotional and cognitive processing
-Disorders such as autism, dyslexia, schizophrenia