Modular output circuits of the fastigial nucleus for diverse motor and nonmotor functions of the cerebellar vermis
- Johns Hopkins University, United States
- Johns Hopkins Medical Institute, United States
Abstract
The cerebellar vermis, long associated with axial motor control, has been implicated in a surprising range of neuropsychiatric disorders and cognitive and affective functions. Remarkably little is known, however, about the specific cell types and neural circuits responsible for these diverse functions. Here, using single-cell gene expression profiling and anatomical circuit analyses of vermis output neurons in the mouse fastigial (medial cerebellar) nucleus, we identify five major classes of glutamatergic projection neurons distinguished by gene expression, morphology, distribution, and input-output connectivity. Each fastigial cell type is connected with a specific set of Purkinje cells and inferior olive neurons and in turn innervates a distinct collection of downstream targets. Transsynaptic tracing indicates extensive disynaptic links with cognitive, affective, and motor forebrain circuits. These results indicate that diverse cerebellar vermis functions could be mediated by modular synaptic connections of distinct fastigial cell types with posturomotor, oromotor, positional-autonomic, orienting, and vigilance circuits.
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All data analyzed during this study are included in the manuscript and supporting files.
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Funding
National Institute of Neurological Disorders and Stroke (NS095232)
- Sascha du Lac
National Institute of Neurological Disorders and Stroke (NS105039)
- Sascha du Lac
Japan Society for the Promotion of Science (26-585)
- Hirofumi Fujita
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures conformed to NIH guidelines and were approved by the Johns Hopkins University Animal Care and Use Committee (M014M28 and M016M464) and Salk Institute Animal Care and Use Committee (11-00024).
Copyright
© 2020, Fujita et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Modular output circuits of the fastigial nucleus for diverse motor and nonmotor functions of the cerebellar vermis
eLife 9:e58613.
https://doi.org/10.7554/eLife.58613
