Striatal mechanisms in Parkinson’s disease: new insights from computer modeling

摘要

We review data and hypotheses concerning the functional anatomy of the striatum and the role of its corticostriatal and nigrostriatal afferents in Parkinson’s disease (PD). Starting from molecular mechanisms of glutamatergic and dopaminergic actions in the striatum we have developed a compartmental model of striatal principal neurons that displays a significant degree of biological realism. Simulations of a network of striatal projection neurons under conditions likely to be found in healthy subjects as well as untreated and therapeutic situations of advanced PD provide clues concerning the dynamics of neuronal interactions and their possible effects on downstream motor structures in the generation of positive and negative motor symptoms. We present tentative biological explanations of the symptoms of rigidity and akinesia in PD leading to predictions concerning the origin of abnormal movements and the beneficial effects of dopaminergic treatment. Although these attempts are not yet sufficient to account for the complexity of clinical symptoms found in PD they can guide further empirical research and foster fruitful interactions between experimentalists, theoreticians, and clinicians in unraveling the functional anatomy of the basal ganglia.