Neurophysiological and behavioral maturation of cerebellar function studied with tremorogenic drugs

Abstract

Harmaline acts on the olivo-cerebello-reticular system to cause tremor. In infant rats, this system is immature. Harmaline-induced tremor develops during the second week of life, at approximately the same age as the climbing fiber synapses on the Purkinje cells assume a morphologically mature form. This suggests that the maturation of the climbing fiber synapses may be a critical event in the functional maturation of the cerebellum. To test this, the effects of harmaline on the behavior and neurophysiology of developing infant rats were studied. A method of probit analysis was developed to compare statistically the age of development of different responses in the rat. Probit analysis showed that neonatal rats developed the ability to tremor in response to harmaline at 9.4 ± 1.8 (mean ± SD) days of age. Using a method for recording from infant rats, the harmaline-induced bursting pattern of cell firing recorded from the cerebellum and inferior olive developed at 9.7 ± 3.8 and 11.0 ± 1.5 days, respectively. There was no statistically significant difference between these three ages. This measurement of the development of harmaline responses represents an accurate timing of developmental events and the direct statistical comparison of the age of occurrence of these events. This study provides a direct statistical comparison of cerebellar development as determined electrophysiologically and behaviorally. The use of harmaline allowed the study of the climbing fiber system specifically, and provided electro-physiological data on inferior olive development. The data indicate that the inferior olive cell becomes functionally mature at 10 days and this development is the critical event in the emergence of harmaline-induced tremor.