Motor Control - Role of the Cerebellum and Basal Ganglia

Question 1

What is the general function of the basal ganglia?

Answer 1

To integrate motor and sensory information from the cortex and relaying the information back to the cortex via the thalamus.

Question 2

List the general functions of the cerebellum.

Answer 2

1 - Coordination of sensory and motor inputs / outputs.

2 - Control of muscle tone.

3 - Motor learning.

Question 3

What is ataxia?

List the functional components of the cerebellum that might cause this symptom.

Answer 3

• Unsteady, staggering gait.

1 - Spinocerebellum.

2 - Pontocerebellum.

3 - Vestibulocerebellum.

Question 4

What is dysmetria?

List the functional components of the CNS that might cause this symptom.

Answer 4

• Inaccurate termination of movement.

1 - Spinocerebellum.

2 - Pontocerebellum.

Question 5

What is hypotonia?

List the functional components of the cerebellum that might cause this symptom.

Answer 5

• Reduced muscle tone.

- Spinocerebellum.

Question 6

What is nystagmus?

List the functional components of the cerebellum that might cause this symptom.

Answer 6

• Involuntary eye movements.

- Vestibulocerebellum.

Question 7

What is dysarthria?

List the functional components of the cerebellum that might cause this symptom.

Answer 7

• Inarticulate speech due to poor oropharyngeal muscle control.
• Pontocerebellum.

Question 8

List the cells and fibres of the cerebellar cortex.

Answer 8

1 - Purkinje cells.

2 - Granule cells.

3 - Parallel fibres.

4 - Climbing fibres.

5 - Mossy fibres.

Question 9

Which cells of the cerebellar cortex constitute most of the output of the cerebellum?

What information do these cells carry?

Answer 9

• Purkinje cells.

- They carry sensory information.

Question 10

With which cells do Purkinje cells synapse?

Answer 10

Deep cerebellar nuclei.

Question 11

What is the function of mossy and climbing fibres?

Answer 11

• They directly convey sensory information to deep cerebellar nuclei.
• They can also convey sensory information to Purkinje cells, which in turn will relay the information to deep cerebellar nuclei.
• Climbing fibres do this directly whereas mossy fibres do this via interneurones known as granule cells.

Question 12

Describe the processing function of deep cerebellar nuclei.

Answer 12

• They compare sensory input before cerebellar processing ( intended movement - obtained by excitatory sensory input via Purkinje cells) and after cerebellar processing (actual movement - obtained by inhibitory sensory input via Purkinje cells).
• If the difference in intended and actual movement is too great, the deep cerebellar nuclei are able to send an efferent compensatory output to the brainstem cortex via the thalamus to adjust the movement.

Question 13

List 3 functions of the cerebellum other than comparing intended and actual movement.

Answer 13

1 - It regulates posture.

2 - It acts as a timer when sequencing motor activation to ensure smooth movement.

3 - It enables motor memory.

Question 14

List 2 diseases caused by damage to the basal ganglia.

Answer 14

1 - Parkinson’s disease.

2 - Huntington’s disease.

Question 15

Describe the cortico-basal ganglia-cortical loop.

Answer 15

1 - The basal ganglia constitutively fire inhibitory neurones which synapse at the ventrolateral thalamus, preventing movement.

2 - The prefrontal cortex sends an excitatory signal to the basal ganglia, causing a pause in inhibitory basal ganglia outflow to the ventrolateral thalamus.

3 - This allows the ventrolateral thalamus to send excitatory signals to the supplementary motor area, causing movement.

Question 16

List the basal ganglia.

Answer 16

• Ventral striatum (vSTR):

1 - Nucleus accumbens.

• Dorsal striatum (dSTR):

1 - Caudate.

2 - Putamen.

• Subthalamic nucleus (STN).
• Globus pallidus (GP):

1 - External segment (GPe).

2 - Internal segment (GPi).

• Substantia nigra (SN):

1 - Reticulata (SNr).

2 - Pars compacta (SNc).

Question 17

Describe the circuitry between the basal ganglia, ventrolateral thalamus and cortex.

Answer 17

No. Try to draw the diagram from the lecture instead.

Just notice that the direct pathway results in increased thalamic activity and the indirect pathway results in decreased thalamic activity.

Question 18

List the basal ganglia that use the glutamate neurotransmitter.

Which other associated structures use glutamate?

How does this reflect their function?

Answer 18

• The subthalamic nucleus if the only nucleus of the basal ganglia that uses glutamate as a neurotransmitter.
• The ventrolateral thalamus and cortex also use glutamate.
• Use of glutamate indicates that these structures are excitatory.

Question 19

List the basal ganglia that use the GABA neurotransmitter.

Which other associated structures use GABA?

Answer 19

1 - Striatum.

2 - External segment of globus pallidus.

3 - Internal segment of globus pallidus.

4 - Substantia nigra reticulata.

• No other associated structures use GABA.
• Use of GABA indicates that these structures are inhibitory.

Question 20

List the basal ganglia that use the dopamine neurotransmitter.

Which other associated structures use dopamine?

Answer 20

• Substantia nigra pars compacta.
• No other associated structures use dopamine.
• Use of dopamine indicates that the substantia nigra is involved in modulation.

Question 21

How does dopamine modulate the outflow of basal ganglia?

Answer 21

• By exciting the direct pathway via excitatory D1 receptors on striato-GPi/SNr neurones to reduce basal ganglia outflow.

or

• By inhibiting the indirect pathway via inhibitory D2 receptors on striato-GPe neurones to reduce basal ganglia outflow.
• Remember the basal ganglia outflow is inhibitory, so reducing outflow increases thalamic activity.

Question 22

Describe the pathophysiology of Parkinson’s disease, Huntington’s, hemiballismus and Tardive dyskinesia.

Answer 22

• Parkinson’s is a result of increased basal ganglia outflow due to degeneration of the substantia nigra, resulting in hypokinesis.
• Huntington’s is a result of decreased basal ganglia outflow due to degeneration of the striatal output neurones in the indirect pathway.
• Hemiballismus is a result of decreased basal ganglia outflow due to degeneration of the subthalamic nucleus.
• Tardive dyskinesia is a result of decreased basal ganglia outflow due to dopamine receptor hypersensitivity.

Question 23

List 3 symptoms of Parkinson’s disease.

Answer 23

1 - Tremor.

2 - Bradykinesia.

3 - Rigidity.

Question 24

List 3 conditions caused by progression of Parkinson’s disease.

Answer 24

1 - Dementia.

2 - Depression.

3 - Bladder disturbance.

Question 25

What are Lewy bodies?

Answer 25

Protein aggregations that are hallmarks of Parkinson’s disease.

Question 26

List 2 treatments for Parkinson’s disease.

Answer 26

1 - Dopamine replacement in the form of L-DOPA, a dopamine precursor (as the substantia nigra is the source of dopamine in the basal ganglia).

2 - Stimulation of the subthalamic nucleus (to turn it off).

Question 27

Why is L-DOPA dosage kept low?

Answer 27

Because sensitivity / tolerance to L-DOPA can decrease with excessive use, so it is given in low doses and supplemented with other drugs that affect dopamine breakdown or reuptake.

Question 28

Why does the effectiveness of L-DOPA decrease naturally with disease progression in Parkinson’s disease?

Answer 28

Because the number of neurones in the substantia nigra decreases with the disease, so:

1 - L-DOPA can’t be used to synthesise dopamine.

2 - There are fewer dopaminergic nerve terminals from which dopamine can be released.

Question 29

Give an example of a side effect of L-DOPA.

Answer 29

L-DOPA-induced dyskinesia.

Question 30

Give an example of a symptom of Huntington’s disease.

Answer 30

Huntington’s chorea.

Question 31

List 2 complications that occur with progression of Huntington’s disease.

Answer 31

1 - Psychiatric disturbance.

2 - Dementia.

Question 32

Which inheritance pattern is shown by Huntington’s disease?

Answer 32

Autosomal dominant.

Question 33

List 3 treatments for Huntington’s disease.

Answer 33

Symptomatic relief:

1 - Tetrabenazine (VMAT inhibitor that decreases dopamine storage and release).

2 - Chlorpromazine (a dopamine antagonist).

3 - Baclofen (a GABA-B agonist that decreases spinal reflexes).

Question 34

What is the most common cause of hemiballismus?

Answer 34

Stroke.

Question 35

What is the primary symptom of hemiballismus?

Answer 35

Violent flailing movements of the contralateral limb.

Question 36

What is the most common cause of Tardive dyskinesia?

Answer 36

Long-term exposure to dopamine receptor antagonists (antipsychotic drugs).