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Parallel organization of cerebellar pathways to sensorimotor, associative, and modulatory forebrain

Thomas J. Pisano, Zahra M. Dhanerawala, Mikhail Kislin, Dariya Bakshinskaya, View ORCID ProfileEsteban A. Engel, Junuk Lee, Nina L. de Oude, Kannan Umadevi Venkataraju, Jessica L. Verpeut, Henk-Jan Boele, Samuel S.-H. Wang
doi: https://doi.org/10.1101/2020.03.06.979153
Thomas J. Pisano
1Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544 USA
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Zahra M. Dhanerawala
1Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544 USA
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Mikhail Kislin
1Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544 USA
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Dariya Bakshinskaya
1Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544 USA
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Esteban A. Engel
1Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544 USA
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  • ORCID record for Esteban A. Engel
Junuk Lee
1Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544 USA
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Nina L. de Oude
2Department of Neuroscience, Erasmus MC, 3000 DR Rotterdam, The Netherlands
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Kannan Umadevi Venkataraju
3Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724 USA
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Jessica L. Verpeut
1Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544 USA
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Henk-Jan Boele
1Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544 USA
2Department of Neuroscience, Erasmus MC, 3000 DR Rotterdam, The Netherlands
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Samuel S.-H. Wang
1Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544 USA
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  • For correspondence: sswang@princeton.edu
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Abstract

Cerebellar outputs take multisynaptic paths to reach higher brain areas, impeding tracing efforts. Here we quantify pathways between cerebellum and contralateral thalamic/corticostriatal structures using the anterograde transsynaptic tracer herpes simplex virus type 1 (H129), the retrograde tracer pseudorabies virus (Bartha), adeno-associated virus, and a whole-brain pipeline for neuron-level analysis using light-sheet microscopy. In ascending pathways, sensorimotor regions contained the most labeled neurons, but higher densities were found in associative areas, including orbital, anterior cingulate, prelimbic, and infralimbic cortex. Ascending paths passed through most thalamic nuclei, especially ventral posteromedial and lateral posterior (sensorimotor), mediodorsal (associative), and reticular (modulatory) nuclei. Retrograde tracing revealed descending paths originating largely from somatomotor cortex. Patterns of ascending influence correlated with anatomical pathway strengths, as measured by brainwide mapping of c-Fos responses to optogenetic inhibition of Purkinje cells. Our results reveal parallel functional networks linking cerebellum to forebrain and suggest that cerebellum uses sensory-motor information to guide both movement and nonmotor functions.

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Posted March 08, 2020.
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Parallel organization of cerebellar pathways to sensorimotor, associative, and modulatory forebrain
Thomas J. Pisano, Zahra M. Dhanerawala, Mikhail Kislin, Dariya Bakshinskaya, Esteban A. Engel, Junuk Lee, Nina L. de Oude, Kannan Umadevi Venkataraju, Jessica L. Verpeut, Henk-Jan Boele, Samuel S.-H. Wang
bioRxiv 2020.03.06.979153; doi: https://doi.org/10.1101/2020.03.06.979153
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Parallel organization of cerebellar pathways to sensorimotor, associative, and modulatory forebrain
Thomas J. Pisano, Zahra M. Dhanerawala, Mikhail Kislin, Dariya Bakshinskaya, Esteban A. Engel, Junuk Lee, Nina L. de Oude, Kannan Umadevi Venkataraju, Jessica L. Verpeut, Henk-Jan Boele, Samuel S.-H. Wang
bioRxiv 2020.03.06.979153; doi: https://doi.org/10.1101/2020.03.06.979153

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