Diverse inhibitory projections from the cerebellar interposed nucleus

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Abstract

The cerebellum consists of parallel circuit modules that contribute to diverse behaviors, spanning motor to cognitive. Recent work employing cell-type specific tracing has identified circumscribed output channels of the cerebellar nuclei that could confer tight functional specificity. These studies have largely focused on excitatory projections of the cerebellar nuclei, however, leaving open the question of whether inhibitory neurons also constitute multiple output modules. We mapped output and input patterns to intersectionally restricted cell types of the interposed and adjacent interstitial nuclei in mice. In contrast to the widespread assumption of primarily excitatory outputs and restricted inferior olive-targeting inhibitory output, we found that inhibitory neurons from this region ramified widely within the brainstem, targeting both motor- and sensory-related nuclei, distinct from excitatory output targets. Despite differences in output targeting, monosynaptic rabies tracing revealed largely shared afferents to both cell classes. We discuss the potential novel functional roles for inhibitory outputs in the context of cerebellar theory.

Data availability

All data analysis is included in the manuscript and supporting files. A related manuscript file (readme) spreadsheet describes the location of source data for figures.

Article and author information

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Elena N Judd

Physiology & Biophysics, University of Colorado School of Medicine, Aurora, United States

Competing interests
The authors declare that no competing interests exist.
Samantha M Lewis

Physiology & Biophysics, University of Colorado School of Medicine, Aurora, United States

Competing interests
The authors declare that no competing interests exist.
Abigail L Person

Physiology & Biophysics, University of Colorado School of Medicine, Aurora, United States

For correspondence
abigail.person@cuanschutz.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9805-7600

Funding

National Institute of Neurological Disorders and Stroke (114430)

Abigail L Person

National Science Foundation (1749568)

Abigail L Person

Simons Foundation (N/A)

Abigail L Person

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 followed the National Institutes of Health Guidelines and were approved by the Institutional Animal Care and Use Committee at the University of Colorado Anschutz Medical Campus under protocol #43, Laboratory of Abigail Person, re-approved 11/2020. Every effort was made to minimize suffering.

Copyright

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.