The basal ganglia operate through two opposing pathways. The direct pathway promotes movement — its activation lets the gate open for a chosen action. The indirect pathway, which we will meet next, suppresses competing alternatives.
Here is the direct pathway in detail. Cortex sends an excitatory glutamatergic projection to the striatum. Striatal direct-pathway neurons (which express D1 dopamine receptors) project inhibitory GABAergic signals to the internal globus pallidus (GPi). GPi normally fires tonically, inhibiting the thalamus. When direct-pathway striatal neurons fire, they inhibit GPi — and because GPi was inhibiting the thalamus, inhibiting GPi disinhibits the thalamus. The thalamus then excites cortex, completing the loop and producing movement.
Walk through that sequence one more time. Cortex excites striatum. Striatum inhibits GPi. GPi normally inhibits thalamus, but with GPi inhibited, the thalamus is freed. The free thalamus excites cortex. The motor program runs.
Two inhibitions in a row produce excitation. This is called disinhibition, and it is one of the most important computational tricks in neural circuits. The basal ganglia use it everywhere.
Dopamine from the substantia nigra modulates the direct pathway through D1 receptors. D1 receptors are excitatory — they make direct-pathway striatal neurons more likely to fire. So dopamine activates the direct pathway, which inhibits GPi, which disinhibits thalamus, which produces movement. Dopamine says go.
When the substantia nigra dies in Parkinson's disease, the direct pathway gets less D1 activation. The gate opens less easily for chosen actions. The patient experiences bradykinesia and difficulty initiating movement. The treatment is levodopa — replace the missing dopamine, and the direct pathway can again activate normally.
Hold this circuit. The direct pathway is a chain of disinhibitions, modulated by dopamine at D1 receptors, that lets the cortex execute its chosen motor program. When you watch a healthy person reach smoothly for a cup, you are watching this circuit work. When you watch a Parkinson's patient struggle to initiate the same movement, you are watching this circuit fail.