In the basal ganglia circuits, the direct pathway is characterized by which neurotransmitter released from the striatum to the globus pallidus internus (GPi)?

Explanation

## Direct Pathway Neurotransmission **Key Point:** The direct pathway from the striatum to the globus pallidus internus (GPi) uses GABA as the primary neurotransmitter, which is inhibitory. ### Mechanism The direct pathway is a monosynaptic inhibitory circuit: - **Striatal medium spiny neurons (MSNs)** express D1 dopamine receptors - These neurons release **GABA** directly onto GPi neurons - GABA is an inhibitory neurotransmitter → hyperpolarizes GPi neurons → reduces their firing - Reduced GPi output → disinhibition of thalamus → facilitation of motor execution ### Direct vs. Indirect Pathway Comparison | Feature | Direct Pathway | Indirect Pathway | |---------|---|---| | **Striatal receptor** | D1 dopamine | D2 dopamine | | **First synapse** | Striatum → GPi (GABA) | Striatum → GPe (GABA) | | **Net effect** | Facilitates movement | Inhibits movement | | **Dopamine action** | Enhances pathway | Suppresses pathway | **High-Yield:** In Parkinson's disease, loss of dopamine reduces D1 pathway activity → decreased motor facilitation → bradykinesia and rigidity. **Clinical Pearl:** The balance between direct (facilitatory) and indirect (inhibitory) pathways determines the net motor output. Dopamine tilts the balance toward the direct pathway.