Inferior olivary-induced expression of Fos-like immunoreactivity in the cerebellar nuclei of wild-type and Lurcher mice

Earlier behavioural studies have shown that the expression of the immediate -early gene c-fos, as visualized by the immunohistochemical detection of Fo s, in the inferior olive (IO) correlated closely with expression in related areas of the cerebellar nuclei. It has been speculated that the expression of c-fos within the cerebellar nuclei may be induced by enhanced spiking a ctivity of the immunopositive neurons in the inferior olive. Two potential mechanisms may play a role in this process: a direct induction by way of th e collaterals of the olivary climbing fibres to the cerebellar nuclei, or i ndirectly, by climbing fibre activity-induced depression of mossy fibre-par allel fibre-induced simple spike frequency of the Purkinje cells resulting in a subsequent disinhibition of the related parts of the cerebellar nuclei . In an attempt to distinguish between these possible mechanisms, we analys ed Fos immunoreactivity in the olivocerebellar system of wild-type mice and in the mutant mouse Lurcher which lacks Purkinje cells. The tremorgenic ag ent harmaline, which is known to induce enhanced and rhythmic firing of oli vary neurons was given intraperitoneally to anaesthetized mice of both geno types. Harmaline application coincides with the induction of Fos-immunoreac tive neurons in most areas of the 10 in both wild-type and Lurcher mice. Bo th types of mice also showed enhanced expression in the larger neurons of t he cerebellar nuclei. However, in the smaller, GABAergic nucleo-olivary neu rons, increased c-fos expression was only observed in the wild-type mice. W e conclude that: (i) increased olivary activity indeed may result in increa sed c-Fos expression in related areas of the cerebellar nuclei; (ii) becaus e the indirect mode of induction is not operative in Lurcher mice, the oliv ary collateral innervation of the cerebellar nuclei is sufficient for c-fos induction in the larger nucleobulbar neurons in Lurcher and potentially al so in wild-type mice; however (iii) for the nucleo-olivary cells an intact cerebellar cortical input is necessary to evoke increased expression of c-f os following harmaline application.