Bradykinesia in Parkinson's disease: direct and indirect pathways
Bradykinesia (slowed movement) in Parkinson's disease results from dopamine loss, which reduces excitation of the direct 'go' pathway and reduces inhibition of the indirect 'no-go' pathway.
Remember
In Parkinson's disease the direct pathway loses its excitation from dopamine and the indirect pathway is held back less, so less drive reaches the cortex and movement is slow.
The basal ganglia (structures known to fine-tune voluntary movements) act through the direct and indirect pathways. The direct pathway is the 'go' route, and it promotes movement. The indirect pathway is the 'no-go' route, and it suppresses unwanted movement.
Dopamine normally helps movement by exciting the direct pathway through D1 receptors and damping the indirect pathway through D2 receptors. The dopamine comes from the substantia nigra pars compacta, a dark band of dopamine-producing cells.
In Parkinson's disease the dopamine-producing (dopaminergic) neurones of that region degenerate. The direct pathway is then excited less, and the indirect pathway, the brake on unwanted movement, is inhibited (held back) less.
The globus pallidus internus (GPi), an output nucleus of the basal ganglia, gives constant inhibition to the thalamus, and the thalamus excites the motor cortex (the cortex that produces voluntary movement). The direct pathway lowers GPi output, whereas the indirect pathway raises it. With dopamine lost, GPi inhibition of the thalamus rises, less drive reaches the cortex, and movement becomes hard to start and slow. The cortex itself is intact but under-driven.
That slowing of movement is bradykinesia.
Key facts
- Cause
- the dopaminergic neurones of the substantia nigra pars compacta degenerate.
- Direct pathway
- dopamine excites it, and it promotes movement.
- Indirect pathway
- dopamine normally inhibits it, and it suppresses unwanted movement.
- Output nucleus
- the globus pallidus internus gives constant inhibition to the thalamus, and dopamine loss raises that inhibition.
- Speech and face
- quiet speech (hypophonia) results from bradykinesia of the larynx, and a mask-like face from bradykinesia of the facial muscles.
- Levodopa
- a treatment that aims to replace dopamine.
Exam traps
- More activity in the direct pathway would not slow movement, because that pathway reduces the inhibition of the thalamus and so promotes movement. Dopamine loss reduces direct pathway activity rather than increasing it.
- Less activity in the indirect pathway does not explain slow movement, because that pathway normally suppresses movement, so less of it releases movement. When dopamine is lost the indirect pathway becomes more active, not less.
- Degeneration of neurones in the globus pallidus internus would not fit slowness, because that nucleus inhibits the thalamus, so thalamic inhibition would fall and movement would increase. In Parkinson's disease the activity of the globus pallidus internus rises rather than being lost.
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