Post-natal development of synaptic connections in the cerebellar cortex of the Reeler mouse

Reelin, an extracellular protein that promotes neuronal migration in the brain areas with laminar architecture, is missing in the Reeler mouse (reeler -/-). Several studies indicate that reelin is also necessary for correct den-drite outgrow and synapse formation in the adult forebrain of mice and humans. More specifically, a Reelin deficit is correlated with a decrease in the number of synaptic contacts and spine density in hippocampus. Our previous observations at the light level in the postnatal and adult reeler -/- mouse cerebellum demonstrated a reduction in size, foliation and cortical lamination. We have characterized here the development and synaptic organization of the cerebellar cortex in P0, P5, P10 and P15 Reeler mice and wild type controls by TEM. Our ultrastructural studies confirmed the existence of deep alterations in cortical architecture with difficulties in identifying the inhibitory interneurons and altered migration of the Purkinje cells that remained deeply embed-ded in the white matter, intermingled with other cortical neurons and the glial cells. There is a general de-crease in the density of the synapses made by the parallel fibers, in the number of the climbing fiber boutons on the Purkinje cells, and in mossy fiber rosettes. Some Purkinje cells are devoid of axo-somatic contacts and surrounded by glial laminae. Examination at different post-natal ages indicates that synaptogenesis requires a longer time in mutant mice but shows very similar morphological features, although decreased in total num-bers when compared to controls. Our results confirm that reelin affect synaptic connectivity in post-natal mouse cerebellum