Temporal sequence of motor disturbances and increased cerebellar glutamic acid decarboxylase activity following 3-acetylpyridine lesions in adult rats

Adult male rats were administered 75 mg/kg of the neurotoxin 3-acetylpyridine to produce lesions of the inferior olive-climbing fiber projection to the cerebellum. At selected times ranging from 6 h to 43 days postlesion, rats were evaluated for motor dysfunction, and glutamic acid decarboxylase (GAD) activity was determined in the deep cerebellar nuclei and cerebellar vermis. In the deep nuclei non-monotonic changes in GAD activity were found following climbing fiber destruction. Initially, there was a steady increase in GAD activity which peaked at 38% above control values 14 days postlesion. GAD activity then slowly declined, although it remained significantly above control levels at 43 days postlesion, the latest time point examined. In the vermis, GAD activity was significantly increased at 4 days postlesion (+8%) and remained at approximately this level throughout the experiment. The initial behavioral effects of climbing fiber loss included hypotonia and ataxia with severely reduced mobility. With time, the ataxia and hypotonia decreased and movements such as mud-walking and pivoting developed. As these behaviors diminished, other novel conditions such as movement-associated tremor and hopping appeared. These results are discussed in the context of the previously reported effects of climbing fiber lesions on the firing rates of Purkinje cells and deep nuclei cells.