Direct translation of climbing fiber burst-mediated sensory coding into post-synaptic Purkinje cell dendritic calcium

  1. Seung-Eon Roh
  2. Seung Ha Kim
  3. Changhyeon Ryu
  4. Chang-Eop Kim
  5. Yong Gyu Kim
  6. Paul F Worley
  7. Sun Kwang Kim
  8. Sang Jeong Kim  Is a corresponding author
  1. Johns Hopkins University School of Medicine, United States
  2. Seoul National University College of Medicine, Korea (South), Republic of
  3. Gachon University College of Korean Medicine, Republic of Korea
  4. Kyoung Hee University College of Korean Medicine, Republic of Korea
  5. Seoul National University College of Medicine, Republic of Korea

Abstract

Climbing fibers (CFs) generate complex spikes (CS) and Ca2+ transients in cerebellar Purkinje cells (PCs), serving as instructive signals. The so-called 'all-or-none' character of CSs has been questioned since the CF burst was described. Although recent studies have indicated a sensory-driven enhancement of PC Ca2+ signals, how CF responds to sensory events and contributes to PC dendritic Ca2+ and CS remains unexplored. Here, single or simultaneous Ca2+ imaging of CFs and PCs in awake mice revealed the presynaptic CF Ca2+ amplitude encoded the sensory input's strength and directly influenced post-synaptic PC dendritic Ca2+ amplitude. The sensory-driven variability in CF Ca2+ amplitude depended on the number of spikes in the CF burst. Finally, the spike number of the CF burst determined the PC Ca2+ influx and CS properties. These results reveal the direct translation of sensory information-coding CF inputs into PC Ca2+, suggesting the sophisticated role of CFs as error signals.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1 through 5. Code has been made available via GitHub at https://github.com/NeuRoh1/Calcium_signal_processing .

Article and author information

Author details

  1. Seung-Eon Roh

    Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Seung Ha Kim

    Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea (South), Republic of
    Competing interests
    The authors declare that no competing interests exist.
  3. Changhyeon Ryu

    Physiology, Seoul National University College of Medicine, Seoul, Korea (South), Republic of
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5207-9142
  4. Chang-Eop Kim

    Physiology, Gachon University College of Korean Medicine, Seongnam, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  5. Yong Gyu Kim

    Department of Physiology, Seoul National University College of Medicine, Seoul, Korea (South), Republic of
    Competing interests
    The authors declare that no competing interests exist.
  6. Paul F Worley

    Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5086-614X
  7. Sun Kwang Kim

    Physiology, Kyoung Hee University College of Korean Medicine, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2649-6652
  8. Sang Jeong Kim

    Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea
    For correspondence
    sangjkim@snu.ac.kr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8931-3713

Funding

National Research Foundation of Korea (2018R1A5A2025964)

  • Sang Jeong Kim

National Research Foundation of Korea (2017M3C7A1029611)

  • Sang Jeong Kim

National Research Foundation of Korea (2016R1D1A1A02937329)

  • Sun Kwang Kim

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#SNU-111214-6-3) of the Seoul National University. The protocol was approved by the Committee on the Ethics of Animal Experiments of the Seoul National Universtiy. All surgery was performed under intraperitoneal injections of Zoletil/Rompun mixture (30 mg / 10 mg/kg), and every effort was made to minimize suffering.

Copyright

© 2020, Roh 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

  • 2,346
    views
  • 339
    downloads
  • 17
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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)

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

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

  1. Seung-Eon Roh
  2. Seung Ha Kim
  3. Changhyeon Ryu
  4. Chang-Eop Kim
  5. Yong Gyu Kim
  6. Paul F Worley
  7. Sun Kwang Kim
  8. Sang Jeong Kim
(2020)
Direct translation of climbing fiber burst-mediated sensory coding into post-synaptic Purkinje cell dendritic calcium
eLife 9:e61593.
https://doi.org/10.7554/eLife.61593

Share this article

https://doi.org/10.7554/eLife.61593

Further reading

    1. Neuroscience
    2. Structural Biology and Molecular Biophysics
    Yangyu Wu, Yangyang Yan ... Fred J Sigworth
    Research Article

    We present near-atomic-resolution cryoEM structures of the mammalian voltage-gated potassium channel Kv1.2 in open, C-type inactivated, toxin-blocked and sodium-bound states at 3.2 Å, 2.5 Å, 3.2 Å, and 2.9 Å. These structures, all obtained at nominally zero membrane potential in detergent micelles, reveal distinct ion-occupancy patterns in the selectivity filter. The first two structures are very similar to those reported in the related Shaker channel and the much-studied Kv1.2–2.1 chimeric channel. On the other hand, two new structures show unexpected patterns of ion occupancy. First, the toxin α-Dendrotoxin, like Charybdotoxin, is seen to attach to the negatively-charged channel outer mouth, and a lysine residue penetrates into the selectivity filter, with the terminal amine coordinated by carbonyls, partially disrupting the outermost ion-binding site. In the remainder of the filter two densities of bound ions are observed, rather than three as observed with other toxin-blocked Kv channels. Second, a structure of Kv1.2 in Na+ solution does not show collapse or destabilization of the selectivity filter, but instead shows an intact selectivity filter with ion density in each binding site. We also attempted to image the C-type inactivated Kv1.2 W366F channel in Na+ solution, but the protein conformation was seen to be highly variable and only a low-resolution structure could be obtained. These findings present new insights into the stability of the selectivity filter and the mechanism of toxin block of this intensively studied, voltage-gated potassium channel.

    1. Neuroscience
    Hans Auer, Donna Gift Cabalo ... Jessica Royer
    Research Article

    The amygdala is a subcortical region in the mesiotemporal lobe that plays a key role in emotional and sensory functions. Conventional neuroimaging experiments treat this structure as a single, uniform entity, but there is ample histological evidence for subregional heterogeneity in microstructure and function. The current study characterized subregional structure-function coupling in the human amygdala, integrating post-mortem histology and in vivo MRI at ultra-high fields. Core to our work was a novel neuroinformatics approach that leveraged multiscale texture analysis as well as non-linear dimensionality reduction techniques to identify salient dimensions of microstructural variation in a 3D post-mortem histological reconstruction of the human amygdala. We observed two axes of subregional variation in this region, describing inferior-superior as well as mediolateral trends in microstructural differentiation that in part recapitulated established atlases of amygdala subnuclei. Translating our approach to in vivo MRI data acquired at 7 Tesla, we could demonstrate the generalizability of these spatial trends across 10 healthy adults. We then cross-referenced microstructural axes with functional blood-oxygen-level dependent (BOLD) signal analysis obtained during task-free conditions, and revealed a close association of structural axes with macroscale functional network embedding, notably the temporo-limbic, default mode, and sensory-motor networks. Our novel multiscale approach consolidates descriptions of amygdala anatomy and function obtained from histological and in vivo imaging techniques.