Basal Ganglia: Anatomy and Pharmacology (Movement Disorder Symposium 1)

Question 1

Name 3 broad things that the basal ganglia modulate.

Answer 1

Movement, cognition, behavior.

Question 2

What is the striatum composed of?

Answer 2

Caudate and putamen

Question 3

What are the two parts of the pallidum?

Answer 3

Globus pallidus internal (media) and externa (lateral)

Question 4

What are the two parts of the substantia nigra?

Answer 4

Pars compacta (SNc) and Pars reticularis (SNr)

Question 5

Where, anatomically is the putamen? (What does “putamen” mean?)

Answer 5

Big, lateral thing in the middle. (“putamen” = fruit)

Question 6

What is just medial to the putamen?

Answer 6

The globus pallidus externa (GPe)

Question 7

Where are subthalamic nuclei and substantia nigra relative to the rest of the basal ganglia?

Answer 7

Medial and caudal.

Question 8

What two parts of the basal ganglia does the internal capsule separate?

Answer 8

Caudate nucleus and putamen.

Question 9

What’s just lateral to the anterior part of the lateral ventricle?

Answer 9

The head of the caudate nucleus.

Question 10

What’s just dorsal to the substantia nigra?

Answer 10

The subthalamic nuclei. (STN)

Question 11

What part of the basal ganglia is just dorsal to the cerebral peduncles?

Answer 11

The substantia nigra.

Question 12

Does the basal ganglia signal directly to the cortex? What path does the flow of information take?

Answer 12

No. Cortex -> striatum -> globus pallidus int. & substantia nigra reticularis -> thalamus -> cortex. (modified, of course, by the other stuff)

Question 13

What kind of signals do the Globus Pallidus Interna (GPi) and Substantia Nigra Reticularis (SNr) send to the thalamus VA/VL?

Answer 13

Inhibitory signals.

Question 14

Describe the direct pathway of basal ganglia signaling? Most importantly, what is the net effect?

Answer 14

Striatum (modified by SNc) inhibits GPi/SNr. Net effect: Movement, because the thalamus is disinhibited.

Question 15

Describe the indirect pathway of basal ganglia signaling? Most importantly, what is the net effect?

Answer 15

Striatum –| GPe –| STN –> GPi/SNr –| thalamus

Net effect: inhibition of muscle output

Question 16

What protein accumulates in Parkinson’s disease? What are cytoplasmic aggregates of it called?

Answer 16

alpha-synuclein. Lewy bodies.

Question 17

When do protein aggregates in Parkinson’s cause symptoms? Does this affect the direct or indirect basal ganglia pathway?

Answer 17

When they reach the substantia nigra (particularly the pars compacta). Messes up the direct pathway -> reduced motor activity.

Question 18

What are the motor signs of Parkinson’s? (name 4)

Answer 18

Bradykinesia (slow movement), rigid movement with increased tone, resting tremors, stooping / unstable posture.

Question 19

Non-motor signs of Parkinsons? (name 5)

Answer 19

depression, constipation, urinary symptoms, sleep disorders, hyposmia

Question 20

What is a surgical therapy for Parkinson’s?

Answer 20

Implant a “stimulator” of the globus pallidus externa (GPe).

Question 21

Pharmalogical therapy for Parkinson’s?

Answer 21

L-DOPA, or dopamine receptor agonist

Question 22

What does Huntington’s disease (HD) affect?

Answer 22

Spiny GABAergic neurons of striatum, whose output is through the indirect pathway

Question 23

Symptoms of HD? (4 things)

Answer 23

Chorea (brief, jerky movements), athetosis (slow, writhing movements), mental decline, personality changes

Question 24

Genetics (what?) review: Mode of inheritance of HD?

Answer 24

autosomal dominant- instability in the CAG repeats… too many -> HD

Question 25

Is weakness a symptom of Parkinson’s?

Answer 25

No.

Question 26

Does dopamine increase or decreased motor output from the basal ganglia?

Answer 26

Dopamine increases motor output

Question 27

Is dopamine excitatory or inhibitory?

Answer 27

Depends on the receptor:
D1 is excitatory
D2 is inhibitory

Question 28

What’s the name of pathway that uses dopamine in the basal ganglia?

Answer 28

Nigrostriatal, because the substantia nigra makes dopamine that acts on the striatum.

Question 29

What is L-DOPA? Why not give L-Tyrosine?

Answer 29

L-DOPA is an intermediate in dopamine synthesis that is after the rate-limiting step. L-tyrosine is before the rate-limiting step.

Question 30

Why give L-DOPA and not dopamine?

Answer 30

L-DOPA can cross the BBB, dopamine can’t as well.

Question 31

What enzyme converts L-DOPA to dopamine? Where is it found?

Answer 31

DDC (L-DOPA decarboxylase). Found on both sides of the BBB.

Question 32

What enzyme converts L-DOPA to 3-O-methyldopa? Where is it found?

Answer 32

COMT. Found on both sides of the BBB?

Question 33

What drugs might you give to inhibit the breakdown of L-DOPA in the periphery? What enzyme do they inhibit? Do these drugs cross the BBB?

Answer 33

carbidopa and benserazide inhibit Dopa Decarboxylase (DDC)

Question 34

What enzyme not found in the periphery breaks down L-DOPA in the CNS? Can you inhibit it with a drug?

Answer 34

MAO-B. Yes, you can inhibit it.

Question 35

What drugs can help some of the symptoms of HD?

Answer 35

Dopamine signaling inhibitors.

Question 36

What are some side effects of L-DOPA administration? Why?

Answer 36

Psychosis, impulsivity. Because dopamine is used in other parts of the brain, esp. the limbic system.