Species-dependence and relationship of morphological and electrophysiological properties in nigral compacta neurons

The use of animal models in studying disorders of dopaminergic transmission in humans, such as Parkinson's disease, depends on the assumption that morphological and electrophysiological properties of dopaminergic neurons in the pars compacta of the substantia nigra are relatively constant from rodents to monkeys and humans. While the electrophysiological properties of nigral dopaminergic neurons are highly characteristic and appear to be remarkably uniform, morphological studies of nigral compacta neurons have shown significant size differences across mammalian species. This discrepancy between morphological and electrophysiological characteristics could be reconciled if scaling of neuronal size between species was such that intrinsic properties and responses to afferent inputs would not be affected. We review the principles of morphological scaling of compacta neurons and address this problem by construction and analysis of specific passive and active membrane models. These demonstrate that the size differences between compacta neurons from rats to primates lead to distinct intrinsic electrophysiological properties and that even conservative scaling is not sufficient to ensure constant activity patterns unless further compensatory mechanisms are present. Comparisons with experimental data show that the electrophysiological properties of compacta neurons are characteristic compared to other neuronal types but less uniform than generally recognized. The available data are not sufficient to prove a specific relationship between morphological and electrophysiological properties of compacta neurons but it is evident that they provide no support to the assumption that dopaminergic neurons have similar properties across mammalian species. Thus, comparative experimental studies are required to establish the validity of animal models for nigral function and pathology in humans.