Direct and indirect pathways in levodopa-induced dyskinesia: A more complex matter than a network imbalance
✍ Scribed by Veronica Ghiglieri; Barbara Picconi; Paolo Calabresi
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 45 KB
- Volume
- 25
- Category
- Article
- ISSN
- 0885-3185
No coin nor oath required. For personal study only.
✦ Synopsis
In Parkinson's disease (PD), altered dopamine receptor stimulation exerts its main effects in the striatum producing changes in input integration that lead to imbalance between direct and indirect striatal output pathways and dysfunctional changes in basal ganglia output. The resulting motor symptoms are effectively treated with a replacement therapy using the dopamine precursor L-3,4-dihydroxyphenylalanine (L-dopa). However, with disease progression, pulsatile stimulation of dopamine receptors lead to broader neuronal destabilization and motor complications develop resulting in dyskinesia, a very disabling hyperkinetic long-term side effect of the L-dopa therapy.
In the effort to investigate the mechanisms underlying the development of dyskinesia, 20 years ago, a model of basal ganglia network, based on two distinct, direct and indirect, pathways, was proposed. This classic model, conceived independently by R.L. Albin and M.R. DeLong, has stimulated the development of increasingly detailed paradigms that could explain the complexity of roles covered by these subcortical structures. However, in the late 90s, it has become clear that the basal ganglia circuit could no longer be considered as a unidirectional linear system that encodes information exclusively through changes in neuronal firing rate but, rather, as a highly organized network in which changes