Topographic organization in the cerebellar nuclei and inferior olive in relation to cerebellar hemispheric lobules in the mouse: Distinction between crus I and neighboring lobules.

The parallel closed-loop topographic connections between subareas of the inferior olive (IO), cerebellar cortex, and cerebellar nuclei (CN) define the fundamental modular organization of the cerebellum. The cortical modules or zones are organized into longitudinal zebrin stripes which are extended across transverse cerebellar lobules. However, how cerebellar lobules, which are related to the cerebellar functional localization, are incorporated into the olivo-cortico-nuclear topographic organization has not been fully clarified. In the present study, we analyzed the lobular topography in the CN and IO by making 57 small bidirectional tracer injections in the lateral zebrin-positive stripes equivalent with C2, D1, and D2 zones in every hemispheric lobule in zebrin stripe-visualized mice. C2, D1, and D2 zones were connected to the lateral part of the posterior interpositus nucleus (lPIN), and caudal and rostral parts of the lateral nucleus (cLN, rLN), respectively, and from the rostral part of the medial accessory olive (rMAO), and ventral and dorsal lamellas of the PO (vPO, dPO), respectively, as reported. Within these areas, crus I was specifically connected to the ventral parts of the lPIN, cLN, and rLN, and from the rostrolateral part of the rMAO and the lateral parts of the vPO and dPO. The results indicated that the cerebellar modules have lobule-related subdivisions and that crus I is topographically distinct from other lobules. We speculate that crus I and crus I-connected subdivisions in the CN and IO are involved more in nonmotor functions than other neighboring areas in the mouse.

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

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. However, the central mechanisms for forming topography need to be clarified. IO neurons and PCs are generated during overlapping periods of a few days in embryonic development. Therefore, we examined whether their neurogenic timing is specifically involved in the olivocerebellar topographic projection relationship. First, we mapped neurogenic 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 IO neurons and PCs by labeling topographic olivocerebellar projection patterns and PC neurogenic 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.