Topological relationship between corticotropin-releasing factor-immunoreactive cerebellar afferents and tyrosine hydroxylase-immunoreactive purkinje cells in a hereditary ataxic mutant, rolling mouse Nagoya

Using immunohistochemistry we examined the distribution of corticotropin-releasing factor-positive cerebellar afferents and the topological relationship between their projections and the distribution of tyrosine hydroxylase-positive Purkinje cells in an ataxic mutant, rolling mouse Nagoya. In the mutants, some climbing fibers were more intensely stained for corticotropin-releasing factor, bur their zonal distribution remained the: same as in non-ataxic littermates (control mice). These climbing fibers arose from the dorsal accessory nucleus, the ventral lamella of principal nucleus, the dorsomedial cell group, the subnucleus A, the beta subnucleus and the ventrolateral protrusion of the inferior olive, since perikarya in these olivary subdivisions were more intensely stained for corticotropin-releasing factor than in controls. Some mossy fiber rosettes in the vermal lobules. the simple lobule, the crus I of ansiform lobule, the copula pyramidis and the flocculus also exhibited corticotropin-releasing factor immunoreactivity and were more densely stained in the mutants than in controls. Double immunostaining for corticotropin-releasing factor and tyrosine hydroxylase in the mutant cerebellum revealed that the distribution of tyrosine hydroxylase-positive Purkinje cells corresponded to terminal fields of corticotropin-releasing factor-positive climbing fibers bur not corticotropin-releasing factor-positive mossy fibers, This study indicated an increased corticotropin-releasing factor immunoreactivity in some climbing or mossy fibers in the cerebellum of rolling mouse Nagoya. We also found that the distribution of tyrosine hydroxylase-positive Purkinje cells corresponded to terminal fields of corticotropin-releasing factor-positive climbing fibers in the mutant cerebellum. As the transcription of the tyrosine hydroxylase gene is facilitated by Ca2+, abnormal tyrosine hydroxylase expression in the mutant Purkinje cells may indicate functional abnormality by alterations in intracellular Ca2+ concentrations. Therefore. we suggest that an increased level of corticotropin-releasing factor in a specific population of climbing fibers may alter the function of their target Purkinje cells. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.