Modulation of Movement by the Cerebellum -- do not like

Question 1

What is the cerebellum?

Answer 1

‘Little brain’

Part of your brain located at the back of your head, just above and behind where your spinal cord connects to your brain itself

It’s a subcortical structure
But it does have its own cortex

Question 2

What are the three layers of the cerebellum?

Answer 2

Molecular layer (top)
Purkinje layer (middle)
Granule layer (bottom)

Question 3

What is the anatomy of the cerebellum?

Answer 3

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 4

What are the three main subdivisions of the cerebellum?

Answer 4

Divided into 3 main parts based on their source 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 - concerned 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 concerened primarily with the vestibulo-ocular reflex and with the regulation of movements that maintain posture and equilibrium

There is also the vermis which is a median strip that covers the midline and is concerned with movements of proximal muscles and regulates certain types of eye movements

Question 5

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

Answer 5

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

Question 6

What connects the cerebellum and the rest of the nervous system?

Answer 6

Three large pathways called cerebellar peduncles

Superior peduncle -> an efferent pathway. The neurons that give rise to this pathway are located in thedeep cerebellar nuclei.
Their axons project to the motor nuclei of the thalamus, which in turn relay signals to circuits of upper motor neurons in the primary motor and premotor divisions of the cerebral cortex.
Efferent axons in the superior peduncle also project directly to upper motor neurons in the deep layers ofthe superior colliculus that control orienting movements ofthe head and eyes.

Middle peduncle -> is an afferent pathway to the cerebellum; most of the cell bodies that give rise to this pathway are in the base of the contralateral pons, where they form the pontine nuclei

Inferior peduncle -> is the smallest but most complex of the cerebellar peduncles, containing multiple afferent and efferent pathways.
Afferent pathways in the inferior peduncle include axons from the vestibular nuclei, the spinal cord, and several regions of the brainstem tegmentum, while efferent pathways project to the vestibular nuclei and the reticular formation

Question 7

What is the role of mossy fibres in the cerebellum?

Answer 7

The bulk of the fibres coming up to the cortex
They convey a huge amount of information from all over the body, visual auditory and rich input

They synapse onto granule cells in the bottom (granular) layer

One single mossy fibre distributes across a wide area

Question 8

What is the role of granule cells in the cerebellum?

Answer 8

Granule cells outnumber mossy fibres by 50:1
Granule cells send their axons to the top (molecular) layer, where they split into two to produce parallel fibres.
These granule cells form synapses with purkinje cells

Question 9

What is the role of purkinje cells in the cerebellum?

Answer 9

Purkinje cells bodies lie in the middle (purkinje cell) layer
All cerebellar output comes out through axons of purkinje cells and these travel back down through the granular layer into the white matter
Each purkinje cell receives 150,000 parallel fibre synapses
The other input that the purkinje cell receives is called climbing fibre input, where climbing fibres are the axons of cells in the inferior olive at the base of the brainstem
The climbing fibre wraps itself around the purkinje cell dendritic tree, forming at least 1000 synapses (all with the same input signal)

Question 10

What inputs moderate the inhibitory activity of Purkinje cells?

Answer 10

GABAergic interneurons
Basket cells
Stellate cells (receives input from the parallel fibres and provides an inhibitory input to the Purkinje cell dendrites)

Question 11

Describe the largest afferent pathway within the cerebellum?

Answer 11

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

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 12

Compare activating of purkinke cells to activation of climbing fibres in terms of spike firing

Answer 12

Parallel fibre input to purkinje cells causes indivudal and spontaneous action potentials called simple spikes -> these have a spontaneous, rapid, and frequent discharge
They are discharged about 50 spikes/sec at rest
If you stimulate parallel fibers then their inputs turn out to be excitatory and you can increase the rate to 200n spikes/sec

This can be contrasted with complex spike discharge
Produced by climbing fibre input e.g. a climbing fibre fires
Its like a simple spike but with some ‘after ripples’ - 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 fibres fire, you get a complex spike, got a really relaible connection here
But, they dont occur very often , they have low frequency of firing compared with simple spike so looks like it has little effect on output

Something doesn’t add up, climbing fibres are wrapped around PC dendrites which have 150,0000 synapses with parallel fibres , so if they act as one enormous synapse how do they have low-frequency firing?

Question 13

What does the cerebellum do?

Answer 13

Insight from cerebellar damage?
Makes many movements inaccurate, slow and uncoordinated

Similar effects to alcohol

We think its to do with making accurate movements

Question 14

How does the cerebellum influence movement?

Answer 14

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

Other parts of the brain issue movement commands and carry them out inaccurately, it is the role of the cerebellum to ensure they are carried out properly

Question 15

Could learning be invovled in accurate movements?

Answer 15

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 16

What did Brindley (1964) suggest?

Answer 16

That 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 their execution

Related to the idea of user-friendliness: automaticity -> freeing up the cerebral cortex

Question 17

What is the Marr-Albus framework?

Answer 17

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 18

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

Answer 18

A synaptic weight (betwee parallel fibre and purkinje cell) is change according to the correlation between the parallel-fibres signal and the error signal conveyed by the climbing fibre

i.e.
if its a positive correlation , you reduce the weight
if its a negative correlation, you 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

its as if the system is treating correlation as causation
if changes in input signals correlate with changes in error signals, then they cause them

Question 19

What is the evidence for the decorrelation learning rule?

Answer 19

Evidence comes from Long Term Depression

If you stimulate parallel fibres at the top of the cortex (molecular layer), we can measure the purkinje cell response
Then what you do is pair stimulation of the climbing fibre with stimulation of the parallel fibre, they are correlated
What happens after that is that the response of the purkinje cell is reduced or depressed for a substantial time

This is consistent with ‘error signal’ idea: parallel fibre signals are positvely correlated with climbing fibre signals

Question 20

What is the evidence this theory works? -VOR

Answer 20

If the retinal image moves visual processing is degraded- some kinds of visual information are irretrievably lost

Image movement would be produced e.g. by head movements that occur when walking

Solution- counter-rotate the eyes to exactly offset the head movement

How does the reflex circuitry know how big an eye comand to send to the eye muscles?
Can alter VOR by using spectaxles that alter the size of the retinal image
Glasses change the gain
After some experience, the gain of the VOR is reset and the eyes move an appropriate distance in relation to head movement, thus compensating for the altered size of the visual image

Question 21

What evidence shows the cerebellum is involved in VOR adaptation?

Answer 21

Flocculus Inactivation prevents VOR adaptation

Copy of eye movemet command goes to flocculus and floccular output affects the junction between the semi-circular canals and the brainstem

This is located on a side path to the main reflex so this wont cause paralysis it’ll just cause movement to become inaccurate

It enables the cerebllum to calibrate these mvoements with the mossy-fibre inputs conveying a copy of the eye movement command and the climbing fibre inputs conveying information about retinal image movement

Question 22

What else is the cerebellum involved in?

Answer 22

Sensory prediction
Active sensing
Emotional and cognitive processing
Disorders such as autism, dyslexia, schizophrenia