SPECIES-DEPENDENCE AND RELATIONSHIP OF MORPHOLOGICAL AND ELECTROPHYSIOLOGICAL PROPERTIES IN NIGRAL COMPACTA NEURONS

The use of animal models in studying disorders of dopaminergic transmi ssion in humans, such as Parkinson's disease, depends on the assumptio n that morphological and electrophysiological properties of dopaminerg ic neurons in the pars compacta of the substantia nigra are relatively constant from rodents to monkeys and humans. While the electrophysiol ogical properties of nigral dopaminergic neurons are highly characteri stic and appear to be remarkably uniform, morphological studies of nig ral compacta neurons have shown significant size differences across ma mmalian species. This discrepancy between morphological and electrophy siological 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 mode ls. These demonstrate that the size differences between compacta neuro ns from rats to primates lead to distinct intrinsic electrophysiologic al properties and that even conservative scaling is not sufficient to ensure constant activity patterns unless further compensatory mechanis ms are present. Comparisons with experimental data show that the elect rophysiological properties of compacta neurons are characteristic comp ared to other neuronal types but less uniform than generally recognize d. The available data are not sufficient to prove a specific relations hip between morphological and electrophysiological properties of compa cta neurons but it is evident that they provide no support to the assu mption that dopaminergic neurons have similar properties across mammal ian species. Thus, comparative experimental studies are required to es tablish the validity of animal models for nigral function and patholog y in humans. (C) 1998 Elsevier Science Ltd.