Fasciculation of Granule Cell Neurites is Responsible for the Perpendicular Orientation of Small Inhibitory Interneurons in Mouse Cerebellar Microexplant Cultures In Vitro

Abstract

To study the cellular and molecular mechanisms involved in the perpendicular orientation of stellate and/or basket cells to the direction of fasciculating granule cell neurites, we have used cultures of microexplants from early postnatal mouse cerebellum that show this cellular behaviour in vitro. When these cultures were maintained in the presence of antibodies to the neural cell adhesion molecules L1 and N-CAM or immunoglobulin-like domains I, II and IV of N-CAM, the resulting decrease or increase in the fasciculation of granule cell neurites changed the perpendicular orientation and morphology of the small inhibitory interneurons. Additives which did not perturb fasciculation did not affect the perpendicular orientation and morphology of stellate and/or basket cells. Furthermore, when perturbation of fasciculation was prevented, neither L1 nor N-CAM antibodies modified the positioning or morphology of interneurons. These observations indicate that ordered fasciculation of granule cell neurites is an important parameter in the perpendicular orientation and elaboration of the typical morphology of the small cerebellar inhibitory interneurons.