Basal Ganglia: Anatomy and Pharmacology (Movement Disorder Symposium 1) Flashcards
Name 3 broad things that the basal ganglia modulate.
Movement, cognition, behavior.
What is the striatum composed of?
Caudate and putamen
What are the two parts of the pallidum?
Globus pallidus internal (media) and externa (lateral)
What are the two parts of the substantia nigra?
Pars compacta (SNc) and Pars reticularis (SNr)
Where, anatomically is the putamen? (What does “putamen” mean?)
Big, lateral thing in the middle. (“putamen” = fruit)
What is just medial to the putamen?
The globus pallidus externa (GPe)
Where are subthalamic nuclei and substantia nigra relative to the rest of the basal ganglia?
Medial and caudal.
What two parts of the basal ganglia does the internal capsule separate?
Caudate nucleus and putamen.
What’s just lateral to the anterior part of the lateral ventricle?
The head of the caudate nucleus.
What’s just dorsal to the substantia nigra?
The subthalamic nuclei. (STN)
What part of the basal ganglia is just dorsal to the cerebral peduncles?
The substantia nigra.
Does the basal ganglia signal directly to the cortex? What path does the flow of information take?
No. Cortex -> striatum -> globus pallidus int. & substantia nigra reticularis -> thalamus -> cortex. (modified, of course, by the other stuff)
What kind of signals do the Globus Pallidus Interna (GPi) and Substantia Nigra Reticularis (SNr) send to the thalamus VA/VL?
Inhibitory signals.
Describe the direct pathway of basal ganglia signaling? Most importantly, what is the net effect?
Striatum (modified by SNc) inhibits GPi/SNr. Net effect: Movement, because the thalamus is disinhibited.
Describe the indirect pathway of basal ganglia signaling? Most importantly, what is the net effect?
Striatum –| GPe –| STN –> GPi/SNr –| thalamus
Net effect: inhibition of muscle output
What protein accumulates in Parkinson’s disease? What are cytoplasmic aggregates of it called?
alpha-synuclein. Lewy bodies.
When do protein aggregates in Parkinson’s cause symptoms? Does this affect the direct or indirect basal ganglia pathway?
When they reach the substantia nigra (particularly the pars compacta). Messes up the direct pathway -> reduced motor activity.
What are the motor signs of Parkinson’s? (name 4)
Bradykinesia (slow movement), rigid movement with increased tone, resting tremors, stooping / unstable posture.
Non-motor signs of Parkinsons? (name 5)
depression, constipation, urinary symptoms, sleep disorders, hyposmia
What is a surgical therapy for Parkinson’s?
Implant a “stimulator” of the globus pallidus externa (GPe).
Pharmalogical therapy for Parkinson’s?
L-DOPA, or dopamine receptor agonist
What does Huntington’s disease (HD) affect?
Spiny GABAergic neurons of striatum, whose output is through the indirect pathway
Symptoms of HD? (4 things)
Chorea (brief, jerky movements), athetosis (slow, writhing movements), mental decline, personality changes
Genetics (what?) review: Mode of inheritance of HD?
autosomal dominant- instability in the CAG repeats… too many -> HD
Is weakness a symptom of Parkinson’s?
No.
Does dopamine increase or decreased motor output from the basal ganglia?
Dopamine increases motor output
Is dopamine excitatory or inhibitory?
Depends on the receptor:
D1 is excitatory
D2 is inhibitory
What’s the name of pathway that uses dopamine in the basal ganglia?
Nigrostriatal, because the substantia nigra makes dopamine that acts on the striatum.
What is L-DOPA? Why not give L-Tyrosine?
L-DOPA is an intermediate in dopamine synthesis that is after the rate-limiting step. L-tyrosine is before the rate-limiting step.
Why give L-DOPA and not dopamine?
L-DOPA can cross the BBB, dopamine can’t as well.
What enzyme converts L-DOPA to dopamine? Where is it found?
DDC (L-DOPA decarboxylase). Found on both sides of the BBB.
What enzyme converts L-DOPA to 3-O-methyldopa? Where is it found?
COMT. Found on both sides of the BBB?
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?
carbidopa and benserazide inhibit Dopa Decarboxylase (DDC)
What enzyme not found in the periphery breaks down L-DOPA in the CNS? Can you inhibit it with a drug?
MAO-B. Yes, you can inhibit it.
What drugs can help some of the symptoms of HD?
Dopamine signaling inhibitors.
What are some side effects of L-DOPA administration? Why?
Psychosis, impulsivity. Because dopamine is used in other parts of the brain, esp. the limbic system.
