1. Neuroscience
Download icon

Different contributions of preparatory activity in the basal ganglia and cerebellum for self-timing

  1. Jun Kunimatsu  Is a corresponding author
  2. Tomoki W Suzuki
  3. Shogo Ohmae
  4. Masaki Tanaka  Is a corresponding author
  1. Hokkaido University School of Medicine, Japan
Research Article
  • Cited 20
  • Views 2,991
  • Annotations
Cite this article as: eLife 2018;7:e35676 doi: 10.7554/eLife.35676

Abstract

The ability to flexibly adjust movement timing is important for everyday life. Although the basal ganglia and cerebellum have been implicated in monitoring of supra- and sub-second intervals, respectively, the underlying neuronal mechanism remains unclear. Here, we show that in monkeys trained to generate a self-initiated saccade at instructed timing following a visual cue, neurons in the caudate nucleus kept track of passage of time throughout the delay period, while those in the cerebellar dentate nucleus were recruited only during the last part of the delay period. Conversely, neuronal correlates of trial-by-trial variation of self-timing emerged earlier in the cerebellum than the striatum. Local inactivation of respective recording sites confirmed the difference in their relative contributions to supra- and sub-second intervals. These results suggest that the basal ganglia may measure elapsed time relative to the intended interval, while the cerebellum might be responsible for the fine adjustment of self-timing.

Article and author information

Author details

  1. Jun Kunimatsu

    Department of Physiology, Hokkaido University School of Medicine, Sapporo, Japan
    For correspondence
    kunimatsu.jun@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8003-0650
  2. Tomoki W Suzuki

    Department of Physiology, Hokkaido University School of Medicine, Sapporo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Shogo Ohmae

    Department of Physiology, Hokkaido University School of Medicine, Sapporo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Masaki Tanaka

    Department of Physiology, Hokkaido University School of Medicine, Sapporo, Japan
    For correspondence
    masaki@med.hokudai.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6177-1314

Funding

Ministry of Education, Culture, Sports, Science, and Technology (17H03539,25119005)

  • Masaki Tanaka

Takeda Science Foundation

  • Masaki Tanaka

Uehara Memorial Foundation

  • Masaki Tanaka

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 experimental protocols were evaluated and approved by the Hokkaido University Animal Care and Use Committee (#13-0114). All surgery was performed under general isoflurane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Naoshige Uchida, Harvard University, United States

Publication history

  1. Received: February 5, 2018
  2. Accepted: July 1, 2018
  3. Accepted Manuscript published: July 2, 2018 (version 1)
  4. Version of Record published: July 17, 2018 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 2,991
    Page views
  • 486
    Downloads
  • 20
    Citations

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

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
    Timothy S Balmer et al.
    Research Article Updated

    Synapses of glutamatergic mossy fibers (MFs) onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC’s large dendritic brush. Using mouse brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate was spontaneous, spike-independent exocytosis from the MF terminal, and its level was dependent on activity of glutamate transporters EAAT1–2. Increasing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission.

    1. Developmental Biology
    2. Neuroscience
    Hiroki Takechi et al.
    Research Article

    Transmembrane protein Golden goal (Gogo) interacts with atypical cadherin Flamingo to direct R8 photoreceptor axons in the Drosophila visual system. However, the precise mechanisms underlying Gogo regulation during columnar- and layer-specific R8 axon targeting are unknown. Our studies demonstrated that the insulin secreted from surface and cortex glia switches the phosphorylation status of Gogo, thereby regulating its two distinct functions. Non-phosphorylated Gogo mediates the initial recognition of the glial protrusion in the center of the medulla column, whereas phosphorylated Gogo suppresses radial filopodia extension by counteracting Flamingo to maintain a one axon to one column ratio. Later, Gogo expression ceases during the midpupal stage, thus allowing R8 filopodia to extend vertically into the M3 layer. These results demonstrate that the long- and short-range signaling between the glia and R8 axon growth cones regulates growth cone dynamics in a stepwise manner, and thus shape the entire organization of the visual system.