Exam 3: Basal Ganglia

Question 1

Function of the basal ganglia?

Answer 1

• Initiates movements via action selection, eye movements, and helps with posture
• Addiction also involves the basal ganglia structure, nucleus accumbens

Question 2

Hypokinetic

Answer 2

rigidity, slowness and difficulty initiating movement. Example: Parkinson’s disease

Question 3

Hyperkinetic

Answer 3

uncontrolled, involuntary movements. Example: Huntington’s disease

Question 4

Striatum

Answer 4

A. Dorsal striatum
- Caudate and putamen
- Separated by the internal capsule white matter tract, but connect via cellular bridges
- Receives almost all input to the basal ganglia
- Motor control and habit learning
B. Ventral striatum
- The nucleus accumbens and the olfactory tubercle.
- Goal directed behavior and reward circuitrY

Question 5

Globus Pallidus

Answer 5

• The globus pallidus lies just medial to the putamen
• The putamen and globus pallidus together are called the lenticular or lentiform nucleus (meaning “lens-shaped”)
• Internal segment
• External segment

Question 6

Substantia Nigra

Answer 6

• Located in the midbrain
  A. Substantia nigra-pars reticulata
• Ventral portion
• Contains cells very similar to those of the internal segment of the globus pallidus. These nuclei are separated by the internal capsule.
  B. Substantia nigra pars compacta
• Dorsal portion
• Contains the darkly pigmented dopaminergic neurons that give this nucleus its name.

Question 7

Subthalamic Nucleus

Answer 7

• Located below the thalamus

- Deep brain stimulation (DBS), is used to treat patients with Parkinson disease.

Question 8

Nucleus Accumbens and Ventral Pallidum

Answer 8

• Considered by some people to be part of the basal ganglia

- Functionally distinct because they primarily mediate motivation and reward, instead of movement

Question 9

Direct Pathway

Answer 9

• Direct pathway– from the striatum to the internal segment of the globus pallidus (Gpi) or the substantia nigra pars reticulata
• Direct pathway = facilitates movement

Question 10

Indirect Pathway

Answer 10

• Indirect pathway– from the striatum to the external segment of the globus pallidus, then to the subthalamic nucleus and then finally to the internal segment of the globus pallidus or the substantia nigra pars reticulata
• Indirect pathway = inhibits movements

Question 11

Parkinson’s Disease

Answer 11

• In Parkinson’s disease, dopamine-contacting neurons in the substantia nigra pars compacta degenerate, which are a part of the nigrostriatal pathway
• Dopamine has excitatory effects on striatal neurons in the direct pathway and inhibitory effects on striatal neurons in the indirect pathway. Normally, this results in a net excitation on the thalamus
• Loss of dopamine leads to net inhibition of the thalamus through both direct and indirect pathways as seen in Parkinson’s

Question 12

How does the nigrostriatal pathway have two different effects on the striatum?

Answer 12

1) Direct pathway striatal neurons have DI dopamine receptors, which depolarize the cell in response to dopamine.
2) Indirect pathway striatal neurons have D2 dopamine receptors, which hyperpolarize the cell in response to dopamine.
3) The nigrostriatal pathway thus has the dual effect of exciting the direct pathway, while simultaneously inhibiting the indirect pathway.

Question 13

Parkinson’s Symptoms

Answer 13

1) Bradykinesia - slowness of movements, with difficulty initiating movement
- Directly due to inhibition of the thalamus
2) Resting tremor
3) Rigidity
4) Postural instability
Interestingly, visual and auditory cues can help restore some movement through mechanisms that are not fully understood

Question 14

Parkinson’s Treatment

Answer 14

A. Treatment with levodopa, which produces increased dopamine in the brain, helps compensate for the lost DA in the substantia nigra
- The degeneration of the SNc neurons cannot be reversed or halted, however, so this treatment is a symptomatic treatment, not a cure
B. Deep brain stimulation - Electrodes placed in the subthalamic nucleus (STN)
- Stimulation at high frequencies actually reduces STN activity
- Reduces the indirect pathway
- Mechanism still not completely understood

Question 15

HUNTington’s Disease (background)

Answer 15

A. Huntington’s disease is caused by a genetic mutation that causes abnormal Huntington protein to be created

• This protein is normally implicated in many biological functions, but abnormal form is detrimental because it is toxic to neurons
• With Huntington’s there is a loss of neurons throughout the cortex, not just in movement-specific areas

Question 16

Huntington’s DiseASE (BAsal ganglia effects)

Answer 16

A. In Huntington’s disease, neurons in the striatum degenerate first.

• However, in the early phases the indirect pathway from the striatum sees more degeneration. This produces excessive movement (hyperkinetic) that are characteristic of Huntington’s
• In later stages of the disease, when the entire striatum is degenerating, the symptoms of Huntington’s actually resemble Parkinson’s (hypokinetic)