STRIATAL MECHANISMS IN PARKINSONS-DISEASE - NEW INSIGHTS FROM COMPUTER MODELING

We review data and hypotheses concerning the functional anatomy of the striatum and the role of its corticostriatal and nigrostriatal affere nts in Parkinson's disease (PD). Starting from molecular mechanisms of glutamatergic and dopaminergic actions in the striatum we have develo ped a compartmental model of striatal principal neurons that displays a significant degree of biological realism. Simulations of a network o f striatal projection neurons under conditions likely to be found in h ealthy subjects as well as untreated and therapeutic situations of adv anced PD provide clues concerning the dynamics of neuronal interaction s and their possible effects on downstream motor structures in the gen eration 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 an d the beneficial effects of dopaminergic treatment. Although these att empts are not yet sufficient to account for the complexity of clinical symptoms found in PD they can guide further empirical research and fo ster fruitful interactions between experimentalists, theoreticians, an d clinicians in unraveling the functional anatomy of the basal ganglia . (C) 1998 Elsevier Science B.V. All rights reserved.