A study of cerebellar inositol 1,4,5-trisphosphate receptor following climbing and parallel fibre deafferentation.

We have examined the influence of climbing fibre and parallel fibre afferent inputs on the inositol 1,4,5-trisphosphate (InsP3) receptor in rat cerebellum. Lesions of the inferior olive-climbing fibre projections to Purkinje cells by 3-acetylpyridine (3-AP) significantly reduced the [3H]InsP3 binding density (-20%) with no apparent changes in the binding affinity 21 days after treatment. No further reduction in binding density was found in rats given a second dose 7 days after the initial injection. A significant reduction in the binding density was evident as early as 7 days post-lesion. However, 3-AP (0.5 mM) failed to inhibit [3H]InsP3 binding in vitro. Cerebellar granule cells were lesioned by two consecutive injections of methylazoxymethanol acetate at birth. In these 60-day-old granuloprival rats, the density and affinity of [3H]InsP3 binding sites in the cerebellum remained comparable to the controls. Since lesions of the climbing fibres increase Purkinje cell activity, we suggest that changes in InsP3 receptor density may reflect an adaptative response to the heightened Purkinje cell activity. In addition, the results also indicate that expression of the InsP3 receptor in the cerebellum is largely independent of the presence of granule cell-parallel fibre synaptic innervation onto the Purkinje cells.