The unusual attention that brain dopamine (DA) has received in the 40 years since its identification in the mammalian CNS is due mainly to two factors: (a) the discovery that in Parkinson's disease (PD) there is a specific deficit of nigrostriatal dopamine; and (b) evidence implicating brain DA in psychotic disorders, especially the schizophrenic syndrome. In this lecture I will review the history and evolution of studies on physiology and pharmacology of dopaminergic synapses. In addition, I will examine hypotheses concerning the functional anatomy of the striatum and the role of its corticostriatal and nigrostriatal afférents in Parkinson's disease. Starting from molecular mechanisms of glutamatergic and dopaminergic actions in the striatum, it seems now plausible to develop neural network models of striatal principal neurons that display a significant degree of biological realism. Simulation 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 provides clues concerning the dynamics of neuronal interactions and their possible effects on downstream motor structures in the generation of positive and negative motor symptoms. These attempts represent the beginning of a new integrative approach to account for the complexity of clinical symptoms found in PD and they can guide further empirical research and foster fruitful interaction between experimentalists, theoreticians and clinicians.
|Number of pages||1|
|Journal||Italian Journal of Neurological Sciences|
|Publication status||Published - 1999|
ASJC Scopus subject areas
- Clinical Neurology