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Input and output organization of the mesodiencephalic junction for cerebro-cerebellar communication

Wang, X;Novello, M;Gao, Z;Ruigrok, TJH;De Zeeuw, CI;

Most studies investigating the impact of the cerebral cortex (CC) onto the cerebellum highlight the role of the pons, which provides the mossy fibers to the cerebellum. However, cerebro-cerebellar communication may also be mediated by the nuclei of the mesodiencephalic junction (MDJ) that project to the inferior olive (IO), which in turn provides the climbing fibers to the molecular layer. Here, we uncover the precise topographic relations of the inputs and outputs of the MDJ using multiple, classical, and transneuronal tracing methods as well as analyses of mesoscale cortical injections from Allen Mouse Brain. We show that the caudal parts of the CC predominantly project to the principal olive via the rostral MDJ and that the rostral parts of the CC predominantly project to the rostral medial accessory olive via the caudal MDJ. Moreover, using triple viral tracing technology, we show that the cerebellar nuclei directly innervate the neurons in the MDJ that receive input from CC and project to the IO. By unraveling these topographic and prominent, mono- and disynaptic projections through the MDJ, this work establishes that cerebro-cerebellar communication is not only mediated by the pontine mossy fiber system, but also by the climbing fiber system.