Basal Ganglia and Parkinson's

Question 1

What are the different basal ganglia?

Answer 1

• neostriatum (caudate nucleus and putamen)
• paleostriatum (globus pallidus)
• subthalamic nucleus
• substantia nigra (pars reticulata and pars compacta)

Question 2

What are the functions and related systems of the basal ganglia?

Answer 2

• smooth movement
• switching behaviour
• reward systems
  Closely related to the thalamus, cortex and limbic system

Question 3

Describe the direct pathway

Answer 3

• motor cortex sends activating signals to neostriatum
• neostriaum is inhibitory so sends inhibitory signals to the GPm once activated halting its activity
• this allows the thalamus to send activating signals to the motor cortex amplifying activity and driving muscle contraction

Question 4

Describe the indirect pathway

Answer 4

• motor cortex sends activating signals to the neostriatum
• neostriatum is inhibitory so sends inhibitory signals to the GPl once activated halting its activity
• this causes activation of the subthalamic nucleus which sends activating signals to the GPm
• this drives inhibition of the thalamus which inhibits movement

Question 5

What is the role of the dopamine pathways?

Answer 5

D1 activates the direct pathway and D2 inhibits the indirect pathway.

D1 and D2 originate from pars compacta of the substantia nigra

Question 6

List the clinical conditions associated with basal ganglia problems and the affected nucleus

Answer 6

• Parkinson’s Disease (deficit in dopaminergic neurons)
• Huntington’s Disease (caudate deficit)
• hemiballism (subthalamic deficit)
• Wilson’s Disease (lenticular-putamen and globus pallidus deficit)

Question 7

Describe the presentation of Parkinson’s Disease

Answer 7

• tremor at rest
• rigidity
• hypomimia
• cognitive decline

Question 8

How does Parkinson’s Disease affect the motor loop?

Answer 8

• degeneration of dopaminergic neurons of substantia nigra pars compacta
• lack of stimulating input driven by dopamine decreases the inhibitory output from the neostriatum of the direct pathway
• this leads to increased indirect stimulation and excessive inhibition of the thalamus
• slows/reduces/stops movement

Question 9

How does Huntington’s Disease affect the motor loop?

Answer 9

• neurons in indirect pathway preferentially affected
• normal dopamine input so normal activation of direct pathway
• however, imbalance due to loss of normal inhibitory component from indirect pathway
• leads to overactivation of the thalamus resulting in forceful and inappropriate movement (dyskinesia/hyperkinesia)

Question 10

Why is dopamine administration not a treatment option for Parkinson’s Disease?

Answer 10

Dopamine cannot pass the BBB therefore a compound that can cross must be given that can degrade and release dopamine into the brain tissue once through the barrier

Question 11

What are the treatment options for Parkinson’s

Answer 11

• levodopa combined with a dopa decarboxylase inhibitor (carbidopa/benserizide)
• selegiline (MAO-B inhibitor)
• tolcapone (COMT)
• dopamine agonist (bromocriptine)
• amantadine (anti-viral)
• ACh antagonists (atropine)
• electrical stimulation of subthalamic/medial GP by electrodes to improve motor dysfunction