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.

Reviewing Editor

  1. Megan R Carey, Champalimaud Foundation, Portugal

Version history

  1. Received: July 30, 2020
  2. Accepted: September 17, 2020
  3. Accepted Manuscript published: September 28, 2020 (version 1)
  4. Version of Record published: October 22, 2020 (version 2)

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

  • 2,115
    Page views
  • 320
    Downloads
  • 7
    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)

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
    Peibo Xu, Jian Peng ... Yuejun Chen
    Research Article

    Deciphering patterns of connectivity between neurons in the brain is a critical step toward understanding brain function. Imaging-based neuroanatomical tracing identifies area-to-area or sparse neuron-to-neuron connectivity patterns, but with limited throughput. Barcode-based connectomics maps large numbers of single-neuron projections, but remains a challenge for jointly analyzing single-cell transcriptomics. Here, we established a rAAV2-retro barcode-based multiplexed tracing method that simultaneously characterizes the projectome and transcriptome at the single neuron level. We uncovered dedicated and collateral projection patterns of ventromedial prefrontal cortex (vmPFC) neurons to five downstream targets and found that projection-defined vmPFC neurons are molecularly heterogeneous. We identified transcriptional signatures of projection-specific vmPFC neurons, and verified Pou3f1 as a marker gene enriched in neurons projecting to the lateral hypothalamus, denoting a distinct subset with collateral projections to both dorsomedial striatum and lateral hypothalamus. In summary, we have developed a new multiplexed technique whose paired connectome and gene expression data can help reveal organizational principles that form neural circuits and process information.

    1. Neuroscience
    Maureen van der Grinten, Jaap de Ruyter van Steveninck ... Yağmur Güçlütürk
    Tools and Resources

    Blindness affects millions of people around the world. A promising solution to restoring a form of vision for some individuals are cortical visual prostheses, which bypass part of the impaired visual pathway by converting camera input to electrical stimulation of the visual system. The artificially induced visual percept (a pattern of localized light flashes, or ‘phosphenes’) has limited resolution, and a great portion of the field’s research is devoted to optimizing the efficacy, efficiency, and practical usefulness of the encoding of visual information. A commonly exploited method is non-invasive functional evaluation in sighted subjects or with computational models by using simulated prosthetic vision (SPV) pipelines. An important challenge in this approach is to balance enhanced perceptual realism, biologically plausibility, and real-time performance in the simulation of cortical prosthetic vision. We present a biologically plausible, PyTorch-based phosphene simulator that can run in real-time and uses differentiable operations to allow for gradient-based computational optimization of phosphene encoding models. The simulator integrates a wide range of clinical results with neurophysiological evidence in humans and non-human primates. The pipeline includes a model of the retinotopic organization and cortical magnification of the visual cortex. Moreover, the quantitative effects of stimulation parameters and temporal dynamics on phosphene characteristics are incorporated. Our results demonstrate the simulator’s suitability for both computational applications such as end-to-end deep learning-based prosthetic vision optimization as well as behavioral experiments. The modular and open-source software provides a flexible simulation framework for computational, clinical, and behavioral neuroscientists working on visual neuroprosthetics.