Topographical Relationship in the Mesodiencephalic Projection to the Inferior Olive Linked With Cerebellar Hemispheric Lobules in Mice

The mesodiencephalic junction (MDJ) is located in a caudorostrally elongated, column-shaped region encompassing the medial accessory oculomotor nucleus and perirubral area. It relays cerebral projections to the rostral subnuclei of the inferior olive (IO), which, in turn, send climbing fibers to the cerebellar hemisphere and receive nucleo-olivary projections from the cerebellar nuclei (CN), forming a parallel, loop-shaped, modular circuitry. However, the topographical organization of the MDJ-IO projection, which may contribute to functional localization within the cerebellar hemisphere, has not been fully elucidated. Here, we analyzed the distribution of labeled neurons in the MDJ in relation to those in the CN by injecting a Lumafluor retrograde tracer into various sites within the rostral IO subnuclei of mice. Injections mainly targeting the lateral or medial parts of the rostral IO subnuclei labeled neurons predominantly in the ventral or dorsal CN, respectively (referred to as v- and d-CN-predominant injection cases). Correspondingly, v-CN-predominant injection cases labeled neurons in the rostromedial, centroventral, and caudolateral regions of the MDJ, collectively termed the "sheathing subarea," whereas d-CN-predominant injection cases labeled neurons primarily in the central "shaft subarea" of the MDJ. Considering the previously reported lobule-related topography among the IO, cerebellar cortex, and CN, the sheathing and shaft subareas of the MDJ are likely to project preferentially to crus I and to other neighboring cerebellar hemispheric lobules, respectively. We speculate that the sheathing subarea of the MDJ is more strongly involved in non-somatosensorimotor cognitive functions than the shaft subarea.