Neurogenic timing of the inferior olive subdivisions is related to the olivocerebellar projection topography

Abstract

Abstract The olivocerebellar projection is organized into an intricate topographical connection from the inferior olive (IO) subdivisions to the longitudinally-striped compartments of cerebellar Purkinje Cells (PCs) to play an essential role in cerebellar coordination and learning. The central mechanisms for the formation of this topography have been unclear. PCs and IO neurons are generated during overlapping periods of a few days in embryonic development. Here we examined whether their generation timing is specifically involved in the formation of the topographical relationship of the olivocerebellar projection. We mapped neuronal generation timing in the entire IO by using the neurogenic-tagging system of Neurog2-CreER (G2A) mice and specific labeling of IO neurons with FoxP2. IO subdivisions were classified into three groups depending on their neurogenic timing range. Then, we examined the relationships in the neurogenic-timing gradient between PCs and IO neurons based on the reported topographic olivocerebellar projection pattern and PC generation timing. Early, intermediate, and late groups of IO subdivisions projected to late, intermediate, and early groups of the cortical compartments, respectively, except for a few particular areas. The results indicated that the olivocerebellar topographic relationship is essentially arranged according to the reverse neurogenic-timing gradients of the origin and target.