1. Neuroscience
Download icon

Diverse inhibitory projections from the cerebellar interposed nucleus

  1. Elena N Judd
  2. Samantha M Lewis
  3. Abigail L Person  Is a corresponding author
  1. University of Colorado School of Medicine, United States
Research Article
  • Cited 0
  • Views 671
  • Annotations
Cite this article as: eLife 2021;10:e66231 doi: 10.7554/eLife.66231

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

Author details

  1. Elena N Judd

    Physiology & Biophysics, University of Colorado School of Medicine, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Samantha M Lewis

    Physiology & Biophysics, University of Colorado School of Medicine, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. 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.
    ORCID icon "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.

Reviewing Editor

  1. Roy V Sillitoe, Baylor College of Medicine, United States

Publication history

  1. Preprint posted: January 1, 2021 (view preprint)
  2. Received: January 4, 2021
  3. Accepted: September 19, 2021
  4. Accepted Manuscript published: September 20, 2021 (version 1)
  5. Version of Record published: September 30, 2021 (version 2)

Copyright

© 2021, Judd 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.

Metrics

  • 671
    Page views
  • 108
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Neuroscience
    P Christiaan Klink et al.
    Research Article Updated

    Population receptive field (pRF) modeling is a popular fMRI method to map the retinotopic organization of the human brain. While fMRI-based pRF maps are qualitatively similar to invasively recorded single-cell receptive fields in animals, it remains unclear what neuronal signal they represent. We addressed this question in awake nonhuman primates comparing whole-brain fMRI and large-scale neurophysiological recordings in areas V1 and V4 of the visual cortex. We examined the fits of several pRF models based on the fMRI blood-oxygen-level-dependent (BOLD) signal, multi-unit spiking activity (MUA), and local field potential (LFP) power in different frequency bands. We found that pRFs derived from BOLD-fMRI were most similar to MUA-pRFs in V1 and V4, while pRFs based on LFP gamma power also gave a good approximation. fMRI-based pRFs thus reliably reflect neuronal receptive field properties in the primate brain. In addition to our results in V1 and V4, the whole-brain fMRI measurements revealed retinotopic tuning in many other cortical and subcortical areas with a consistent increase in pRF size with increasing eccentricity, as well as a retinotopically specific deactivation of default mode network nodes similar to previous observations in humans.

    1. Developmental Biology
    2. Neuroscience
    Eduardo Loureiro-Campos et al.
    Research Article

    The transcription factor activating protein two gamma (AP2γ) is an important regulator of neurogenesis both during embryonic development as well as in the postnatal brain, but its role for neurophysiology and behavior at distinct postnatal periods is still unclear. In this work, we explored the neurogenic, behavioral, and functional impact of a constitutive and heterozygous AP2γ deletion in mice from early postnatal development until adulthood. AP2γ deficiency promotes downregulation of hippocampal glutamatergic neurogenesis, altering the ontogeny of emotional and memory behaviors associated with hippocampus formation. The impairments induced by AP2γ constitutive deletion since early development leads to an anxious-like phenotype and memory impairments as early as the juvenile phase. These behavioral impairments either persist from the juvenile phase to adulthood or emerge in adult mice with deficits in behavioral flexibility and object location recognition. Collectively, we observed a progressive and cumulative impact of constitutive AP2γ deficiency on the hippocampal glutamatergic neurogenic process, as well as alterations on limbic-cortical connectivity, together with functional behavioral impairments. The results herein presented demonstrate the modulatory role exerted by the AP2γ transcription factor and the relevance of hippocampal neurogenesis in the development of emotional states and memory processes.