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Basal Ganglia - High Yield Facts + USMLE Pearls

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1. Anatomy & Components

Pearl: The striatum is the INPUT station; GPi + SNr are the OUTPUT stations. The basal ganglia do NOT project directly to the spinal cord - everything goes via thalamus (VA/VL) back to cortex.

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2. The Two Motor Pathways

Direct Pathway (net EXCITATORY to cortex - promotes movement)

Cortex → Striatum --(GABA)--> GPi/SNr --(GABA)--> Thalamus (VA/VL) --(Glu)--> Motor cortex

• Striatum inhibits GPi/SNr → less inhibition of thalamus → thalamus activates cortex
• Net effect: excitatory (two inhibitory synapses = net excitation)
• Striatal neurons express D1 receptors - dopamine stimulates this pathway

Indirect Pathway (net INHIBITORY to cortex - suppresses movement)

Cortex → Striatum --(GABA)--> GPe --(GABA)--> STN --(Glu)--> GPi/SNr --(GABA)--> Thalamus → Cortex

• Striatum inhibits GPe → less inhibition of STN → STN excites GPi/SNr → more inhibition of thalamus → less cortical activation
• Net effect: inhibitory (three inhibitory synapses = net inhibition)
• Striatal neurons express D2 receptors - dopamine inhibits this pathway

USMLE Pearl: Dopamine (via SNc) excites direct pathway (D1) AND inhibits indirect pathway (D2) - both actions result in net increased movement. Loss of dopamine = decreased movement (Parkinson's).

Pearl: Direct pathway neurons co-localize substance P; indirect pathway neurons co-localize enkephalin - histopathology can differentiate them.

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3. Five Parallel Circuits

1. Motor (putamen) - voluntary movement
2. Oculomotor (caudate body) - saccadic eye movements
3. Dorsolateral prefrontal (caudate head) - executive function, working memory
4. Lateral orbitofrontal - behavior, personality
5. Limbic/anterior cingulate (ventral striatum/nucleus accumbens) - motivation, emotion, reward

Pearl: This explains why basal ganglia disorders have both motor AND psychiatric/cognitive features (e.g., OCD, depression, cognitive decline in Huntington's and Parkinson's).

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4. Key Diseases

Parkinson's Disease

• Pathology: Degeneration of SNc dopaminergic neurons; Lewy bodies (alpha-synuclein aggregates)
• Effect on circuits: Loss of dopamine → reduced direct pathway excitation + reduced indirect pathway inhibition → net inhibition of thalamus → bradykinesia
• Symptoms: Resting tremor ("pill-rolling"), rigidity (cogwheel), bradykinesia, postural instability
• Treatment: L-DOPA (dopamine precursor), dopamine agonists (bromocriptine, pramipexole), MAO-B inhibitors (selegiline), anticholinergics (trihexyphenidyl - for tremor)

USMLE Pearls:

• Parkinson's = hypokinetic disorder - substantia nigra loss
• L-DOPA needs peripheral decarboxylase inhibitor (carbidopa) to prevent peripheral conversion
• Anticholinergics work because ACh from striatal interneurons excites the indirect pathway - blocking ACh reduces excess indirect pathway activity
• Deep brain stimulation targets the STN or GPi

Huntington's Disease

• Pathology: CAG trinucleotide repeat expansion on chromosome 4p (huntingtin gene); autosomal dominant; anticipation
• Neurons lost: Striatal GABAergic + cholinergic neurons of the indirect pathway affected FIRST (enkephalin-containing)
• Effect on circuits: Loss of striatal inhibition of GPe → GPe inhibits STN → STN less active → less GPi inhibition → thalamus over-activated → hyperkinesis
• Symptoms: Chorea (early), dementia, psychiatric symptoms (depression, personality change)
• Late stage: Both pathways degenerate → rigid Parkinsonian state

USMLE Pearls:

• Huntington's = hyperkinetic disorder - indirect pathway neurons lost first
• Caudate atrophy on MRI → loss of caudate bulge → "box-car" lateral ventricles
• No cure; tetrabenazine (VMAT2 inhibitor) for chorea - depletes dopamine/serotonin

Hemiballismus

• Pathology: Lesion of the contralateral STN (most often lacunar stroke; also seen in hyperglycemia/hyperosmolar state)
• Mechanism: Damaged STN → less excitation of GPi → less thalamic inhibition → excessive movement
• Symptoms: Wild flinging/flailing movements of contralateral proximal limb (arm > leg)
• Treatment: Haloperidol or other dopamine blockers

USMLE Pearl: Hemiballismus = contralateral STN lesion. Most common cause = lacunar infarct. Can also occur in non-ketotic hyperglycemia.

Wilson's Disease (Hepatolenticular Degeneration)

• Copper accumulation in lenticular nucleus (putamen + globus pallidus) and liver
• AR; ATP7B mutation (chromosome 13)
• Presents with: dysarthria, tremor, choreoathetosis, psychiatric changes + liver disease + Kayser-Fleischer rings
• Low ceruloplasmin, elevated urine copper

USMLE Pearl: Wilson's = basal ganglia + liver. Look for young patient with movement disorder + liver disease + psychiatric symptoms.

Other Disorders

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5. Neurotransmitter Quick Reference

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6. USMLE Summary Table

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7. High-Yield One-Liners

• Input to BG = striatum (caudate + putamen), receives glutamatergic cortical input
• Output of BG = GPi + SNr → VA/VL thalamus → motor cortex (all GABA)
• Direct pathway = excitatory net effect on cortex (promotes movement)
• Indirect pathway = inhibitory net effect on cortex (suppresses movement)
• Dopamine pushes the balance toward movement (excites direct, inhibits indirect)
• STN lesion = hemiballismus (hyperkinetic, contralateral)
• SNc degeneration = Parkinson's (hypokinetic)
• Caudate/putamen degeneration = Huntington's (hyperkinetic early, hypokinetic late)
• Nucleus accumbens = reward, addiction
• BG disorders show ipsilateral deficits? NO - basal ganglia disorders affect the contralateral side
• Cerebellum vs BG: both modulate movement but never project directly to spinal cord - BG uses VA/VL thalamus, cerebellum uses VL/VPLc

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