A role of secretin in postnatal development of purkinje cells

Abstract

Postnatal development of Purkinje cells is one of the fundamental cellular events involved in the coordinated cerebellar development and has been implicated in the pathogenesis of psychiatric disorders. To obtain the distinctive morphology and carry out their dominant role in the cerebellar circuit, Purkinje cells form a single lamina at the early postnatal stage, and develop their spectacular dendritic trees thereafter. Our previous studies have reported that in the cerebellum, secretin (SCT) plays a role in mediating synaptic transmission in the basket cell-Purkinje cell circuit. In Purkinje cell-specific SCT knockout mice, SCT deprivation from Purkinje cells resulted in impaired motor coordination and motor learning function. Here we investigated the role of SCT in postnatal development of Purkinje cells. During the early postnatal period, we found prominent and almost exclusive SCT expression in the soma and proximal dendrites of Purkinje cells while SCT receptor (SCTR) was expressed in Purkinje cell soma only. Using immunofluorescent labelling with Purkinje cell marker Calbindin D28K, the Purkinje cell density was reduced under SCT deprivation. Furthermore, to investigate the dendritic morphology of individual Purkinje cells, cerebellar tissue from SCT knockout (Sct-/-) and age-matched control mice was processed by the Golgi staining and Purkinje cell dendritic anatomy was quantified using sholl analysis. In all measures, Sct-/- mice demonstrated significant reductions in dendritic complexity and dendritic spine density compared with controls. Results of this study illustrated a novel function of SCT in the postnatal development of Purkinje cells, emphasizing the necessary role of SCT in cerebellar-related functions.