L10 - Motor Control: Role of the Cerebellum & 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

What are the general functions of the cerebellum?

Answer 2

• Regulate posture indirectly by adjusting output of major descending motor pathways - control of muscle tone
• Comparator - identifies & corrects discrepancies between intended & actual movement = sensorimotor coordination
• Timer - sequences motor activation resulting in smooth performance
• Role in motor memory

Question 3

What might damage to the spinocerebellum result in?

Answer 3

• Ataxia (unsteady, staggering gait)
• Dysmetria (inaccurate termination of movement)
• Hypotonia (reduced muscle tone)

Question 4

What might damage to the vestibulocerebellum result in?

Answer 4

• Ataxia (unsteady, staggering gait)
• Slow saccades (fast tracking ocular movement impaired)
• Nystagmus (‘dancing eyes’ due to failed vestibulo-oculomotor integration - failed coordination of eye movements)

Question 5

What might damage to the cerebro-(ponto-)cerebellum result in?

Answer 5

• Ataxia (unsteady, staggering gait)
• Dysmetria (inaccurate termination of movement)
• Dysarthria (inarticulate speech due to poor oropharyngeal muscular control)

Question 6

List the cells and fibres of the cerebellar cortex.

Answer 6

1 - Purkinje cells

2 - Granule cells

3 - Parallel fibres

4 - Climbing fibres

5 - Mossy fibres

Question 7

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

What information do these cells carry?

Where do they synapse?

Answer 7

• Purkinje cells
• They carry sensory information
• They synapse with deep cerebellar nuclei

Question 8

What is the function of mossy and climbing fibres?

Answer 8

• 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 9

Describe the processing function of deep cerebellar nuclei.

Answer 9

• 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 10

Describe the cortico-basal ganglia-cortical loop.

Answer 10

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 11

List the basal ganglia.

Answer 11

• Striatum (STR):

1 - Nucleus accumbens

2 - Caudate nucleus

3 - 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 12

How does dopamine modulate the outflow of basal ganglia?

Answer 12

Reinforces direct pathway:

• Dopamine from SNc acts on excitatory D1 receptors on striato-SNr/GPi neurons -> promotes direct pathway -> reduces basal ganglia output -> facilitates movement

Suppresses indirect pathway:

• Dopamine acts on inhibitory D2 receptors on striato-GPe neurons -> prevents inhibition of GPe -> reduced STN activity -> reduced basal ganglia output -> facilitates movement

Question 13

Describe the pathophysiology of Parkinson’s disease.

Answer 13

• Progressive loss (>80%) of nigro-striatal dopaminergic neurons -> excessive inhibition of thalamocortical pathway
• Direct pathway: reduced -> increased inhibitory output
• Indirect pathway: increased -> increased inhibition of GPe -> increased STN activity -> increased inhibitory output

Question 14

What are the issues with using L-DOPA as a treatment for Parkinson’s?

Answer 14

• Effectiveness diminishes over 2-5yrs primarily due to progressive nature of disease -> ↓DA-ergic nerve terminals & ↓capacity to convert L-DOPA to dopamine -> ↑L-DOPA dose &/or frequency
• Consequences: development of dyskinesias; on-off effect – sudden transitions between symptom relief & hypokinesia

Question 15

Describe the pathophysiology of Huntington’s disease.

Answer 15

• Autosomal dominant loss of inhibitory neurones projecting from striatum to GPe -> greater STN inhibition -> decreased basal ganglia output to thalamus
• Overactive thalamocortical pathway -> spontaneous firing -> excessive choreiform movement, & uncontrollable, relatively rapid motor patterns that disrupt normal motor activity

Question 16

What treatments are available for Huntington’s disease?

Answer 16

Symptomatic relief only:

• Tetrabenazine = VMAT inhibitor -> ↓DA storage & release
• Chlorpromazine = DA antagonist
• Baclofen (intrathecal) = GABAB agonist -> ↓ spinal reflexes

Question 17

What is hemiballismus?

Answer 17

Damage to STN usually due to unilat stroke resulting in violent flailing contralat movements of limbs

Question 18

What is Tardive dyskinesia?

Answer 18

• ↑DA receptor sensitivity due to long term exposure to antipsychotic drugs (dopamine receptor antagonists)
• Leading to uncontrolled movement especially of facial & trunk muscles (extrapyramidal effects)