Regarding the direct and indirect pathways of the basal ganglia, all of the following statements are correct EXCEPT:

Explanation

## Direct vs. Indirect Pathways in Basal Ganglia ### Pathway Origins and Architecture **Key Point:** The direct and indirect pathways originate from DISTINCT populations of medium spiny neurons in the striatum, not the same population. This is a fundamental principle of basal ganglia circuitry. - **Direct pathway neurons** express D1 dopamine receptors and project directly to the substantia nigra pars reticulata (SNr) and globus pallidus internus (GPi) - **Indirect pathway neurons** express D2 dopamine receptors and project to the globus pallidus externus (GPe), which then projects to the subthalamic nucleus (STN) ### Functional Consequences | Feature | Direct Pathway | Indirect Pathway | |---------|---|---| | **Origin** | D1+ medium spiny neurons | D2+ medium spiny neurons | | **Primary target** | SNr/GPi (monosynaptic) | GPe (monosynaptic) | | **Net effect on thalamus** | Disinhibition (facilitates movement) | Increased inhibition (suppresses movement) | | **DA effect** | D1 agonism → pathway activation | D2 agonism → pathway inhibition | ### Clinical Pearl **High-Yield:** In Parkinson's disease, dopamine loss causes: - Reduced D1 signaling → **decreased** direct pathway activity → less thalamic disinhibition - Reduced D2 signaling → **increased** indirect pathway activity → more thalamic inhibition - **Net result:** Bradykinesia and rigidity (movement suppression) This explains why dopamine replacement (L-DOPA) restores the balance. ### Why the Distractors Are Correct 1. **Direct pathway facilitates movement** — Correct. D1 activation → SNr/GPi inhibition → thalamic disinhibition → movement facilitation [cite:Kandel 6e Ch 41] 2. **Indirect pathway suppresses movement** — Correct. D2 activation → GPe inhibition → STN disinhibition → increased SNr/GPi output → thalamic inhibition 3. **Monosynaptic projections** — Correct. Direct: striatum → SNr/GPi (one synapse). Indirect: striatum → GPe → STN → SNr/GPi (three synapses, but first step is monosynaptic) **Mnemonic:** **D1-Direct-Disinhibit** (D1 agonists activate direct pathway → facilitate movement); **D2-Delay** (D2 agonists activate indirect pathway → suppress movement)