Basal Ganglia

Question 1

Thalamus

Answer 1

STIMULATES MOVEMENT

by stimulating motor cortex

Question 2

Globus Pallidus internus

Answer 2

INHIBITS MOVEMENT

by inhibiting thalamus

Question 3

Subthalamic Nucleus

Answer 3

INHIBITS MOVEMENT

by stimulating globus pallidus interna, which inhibits thalamus

Question 4

Globus Pallidus externus

Answer 4

STIMULATES MOVEMENT

by inhibiting subthalamic nucleus, blocking its stimulation of GPi, releasing its inhibition of thalamus

Question 5

Striatum 2 Components

Answer 5

Putamen (motor) and caudate (cognitive)

Question 6

Lentiform nucleus 2 Components

Answer 6

Putamen + globus pallidus

Question 7

Striatum Direct Pathway

Answer 7

STIMULATES MOVEMENT

by inhibiting globus pallidus internus, releasing its inhibition on thalamus

Question 8

Stiatum Indirect Pathway

Answer 8

INHIBITS MOVEMENT

by inhibiting GPe, releasing its inhibition of subthalamic nucleus, allowing it to stimulate GPi and inhibit thalamus

Question 9

Substantia Nigra Pars Compacta

Answer 9

STIMULATES MOVEMENT
Releases DA into striatum onto:
Stimulatory D1Rs in direct pathway
Inhibitor D2Rs in indirect pathway

Question 10

Parkinson disease (what it is, histo, 5 symptoms)

Answer 10

Degenerative loss of DA neurons (depigment) of substantia nigra pars compacta associated with Lewy bodies (alpha-synuclein - intracellular eosinophilic inclusions)
TRAPS:
Tremor (pilling rolling tremor at rest, early sign)
Rigidity (cogwheel)
Akinesia (or bradykinesia)/trouble initiating
Postural instability
Shuffling gait

Question 11

Huntington Disease (what it is, genetics, 3 NTs, age, radiograph)

Answer 11

Lotsa C’s
AD trinucleotide repeat CAG disorder on chromosome 4
Increase DA, decrease GABA, decrease ACh, causes neuronal death via NMDA-binding/glutamate toxicity w/ atrophy of caudate nuclei with ex vacuo dilatation of frontal horns on MRI
Choreiform movements w/ aggression and dementia, around age 40

Question 12

Athetosis

Answer 12

Slow writing movements, esp. fingers, found in Huntington

Question 13

Levodopa (what it is and problems)

Answer 13

Can cross BBB, converted by dopa decarboxylase in brain to treat Parkinson’s disease. Can get arrhythmias from peripheral metabolism, also hallucinations/psychosis stuff. Resistance leads to akinesia between doses

Question 14

Carbidopa

Answer 14

Inhibits Dopa decarboxylase in periphery so give it with Levodopa to reduce side effects

Question 15

Selegiline

Answer 15

Selectively inhibits MAO-B which preferentially metabolizes DA, for PD. Really good for MPTP exposure because blocks conversion to MPP

Question 16

2/3 DA Agonists

Answer 16

Ergot (peripheral vasoconstriction) - bromocriptine

Non-ergot (preferred) - pramixpexole, ropinirole

Question 17

Amantadine

Answer 17

PD. Previously used as an antiviral, increases DA release and decreases DA uptake. Can cause ataxia and livedo reticularis

Question 18

Tolcapone

Answer 18

Blocks L-Dopa/DA breakdown by inhibiting COMT, so often given as triple therapy with L-dopa and carbidopa

Question 19

Benzotropine

Answer 19

Antimuscarinic (bc high ACh) so improves tremor and rigidity but has little effect on bradykinesia

Question 20

Deep Brain Stimulation

Answer 20

Treatment for Parkinson’s, overstimulate subthalamic nucleus causing its deactivation, releasing its inhibition of movement

Question 21

3 Huntington Disease Drugs

Answer 21

Haloperidol - D2R antagonist, help with psychosis too (neuroleptics, can also use olanzapine)
Tetrabenazine and reserpine - inhibit vesicular monoamine transporter (VMAT) to limit DA vesicle packaging and release