FASCICULATION OF GRANULE CELL NEURITES IS RESPONSIBLE FOR THE PERPENDICULAR ORIENTATION OF SMALL INHIBITORY INTERNEURONS IN MOUSE CEREBELLAR MICROEXPLANT CULTURES IN-VITRO

To study the cellular and molecular mechanisms involved in the perpend icular orientation of stellate and/or basket cells to the direction of fasciculating granule cell neurites, we have used cultures of microex plants from early postnatal mouse cerebellum that show this cellular b ehaviour in vitro. When these cultures were maintained in the presence of antibodies to the neural cell adhesion molecules L1 and N-CAM or i mmunoglobulin-like domains I, II and IV of N-CAM, the resulting decrea se or increase in the fasciculation of granule cell neurites changed t he perpendicular orientation and morphology of the small inhibitory in terneurons. Additives which did not perturb fasciculation did not affe ct the perpendicular orientation and morphology of stellate and/or bas ket cells. Furthermore, when perturbation of fasciculation was prevent ed, neither L1 nor N-CAM antibodies modified the positioning or morpho logy of interneurons, These observations indicate that ordered fascicu lation of granule cell neurites is an important parameter in the perpe ndicular orientation and elaboration of the typical morphology of the small cerebellar inhibitory interneurons.