REGIONAL BRAIN VARIATIONS OF CYTOCHROME-OXIDASE ACTIVITY AND MOTOR COORDINATION IN LURCHER MUTANT MICE

Lurcher mutant mice are characterized by massive degeneration of cereb ellar Purkinje cells and granule cells and by deficits in motor coordi nation. Regional brain variations of cytochrome oxidase (CO) activity were analyzed to identify those brain regions with abnormal metabolic activity as a secondary consequence of the cerebellar atrophy and to e stablish the relationship between CO activity and motor deficits. Lurc her mutants had higher CO activity in all three cerebellar deep nuclei than normal littermate controls of the same background strain. Higher CO activity was also found in Lurcher mutants in brain regions direct ly connected to the cerebellum, such as the lateral vestibular nucleus , the cochlear nucleus, the red nucleus, the ventrolateral thalamus, t he dorsal raphe, the interpeduncular nucleus, and the inferior collicu lus. By contrast, there was a sharp decrease in CO activity in the inf erior olive. As for brain regions not directly connected to the cerebe llum, higher CO activity was observed in the trigeminal motor nucleus and the CA1 molecular layer of the hippocampus, which highlights proba ble transsynaptic alterations as a secondary consequence of cerebellar atrophy. A positive correlation between CO activity in the red nucleu s and latencies before falling in two motor-coordination tests indicat es that a compensatory increase of metabolic activity in a cerebellar efferent region is associated with improved behavior.