1. Neuroscience
Download icon

Precisely-timed dopamine signals establish distinct kinematic representations of skilled movements

  1. Alexandra Bova
  2. Matt Gaidica
  3. Amy Hurst
  4. Yoshiko Iwai
  5. Julia Hunter
  6. Daniel K Leventhal  Is a corresponding author
  1. University of Michigan, United States
Research Article
  • Cited 0
  • Views 500
  • Annotations
Cite this article as: eLife 2020;9:e61591 doi: 10.7554/eLife.61591

Abstract

Brain dopamine is critical for normal motor control, as evidenced by its importance in Parkinson Disease and related disorders. Current hypotheses are that dopamine influences motor control by 'invigorating' movements and regulating motor learning. Most evidence for these aspects of dopamine function comes from simple tasks (e.g., lever pressing). Therefore, the influence of dopamine on motor skills requiring multi-joint coordination is unknown. To determine the effects of precisely-timed dopamine manipulations on the performance of a complex, finely coordinated dexterous skill, we optogenetically stimulated or inhibited midbrain dopamine neurons as rats performed a skilled reaching task. We found that reach kinematics and coordination between gross and fine movements progressively changed with repeated manipulations. However, once established, rats transitioned abruptly between aberrant and baseline reach kinematics in a dopamine-dependent manner. These results suggest that precisely-timed dopamine signals have immediate and long-term influences on motor skill performance, distinct from simply 'invigorating' movement.

Article and author information

Author details

  1. Alexandra Bova

    Neuroscience Graduate Program, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Matt Gaidica

    Neuroscience Graduate Program, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Amy Hurst

    Neurology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yoshiko Iwai

    Neurology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Julia Hunter

    Neurology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Daniel K Leventhal

    Neurology, University of Michigan, Ann Arbor, United States
    For correspondence
    dleventh@med.umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8174-5933

Funding

National Institute of Neurological Disorders and Stroke (K08-NS072183)

  • Daniel K Leventhal

Nvidia (GPU grant)

  • Daniel K Leventhal

University of Michigan

  • Daniel K Leventhal

Brain Research Foundation (BRF Seed Grant)

  • Daniel K Leventhal

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 an approved institutional animal care and use committee (IACUC) protocol (#8407) of the University of Michigan. All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Aryn H Gittis, Carnegie Mellon University, United States

Publication history

  1. Received: July 30, 2020
  2. Accepted: November 24, 2020
  3. Accepted Manuscript published: November 27, 2020 (version 1)

Copyright

© 2020, Bova 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

  • 500
    Page views
  • 115
    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
    María Fernanda López-Gutiérrez et al.
    Research Article

    Previous studies have related pair bonding in Microtus ochrogaster, the prairie vole, with plastic changes in several brain regions. However, the interactions between these socially-relevant regions have yet to be described. In this study, we used resting state magnetic resonance imaging to explore bonding behaviors and functional connectivity of brain regions previously associated with pair bonding. Thirty-two male and female prairie voles were scanned at baseline, 24h and 2 weeks after the onset of cohabitation By using network based statistics, we identified that the functional connectivity of a cortico-striatal network predicted the onset of affiliative behavior, while another predicted the amount of social interaction during a partner preference test. Furthermore, a network with significant changes in time was revealed, also showing associations with the level of partner preference. Overall, our findings revealed the association between network-level functional connectivity changes and social bonding.

    1. Developmental Biology
    2. Neuroscience
    Alessia Caramello et al.
    Research Article Updated

    During embryonic development, radial glial cells give rise to neurons, then to astrocytes following the gliogenic switch. Timely regulation of the switch, operated by several transcription factors, is fundamental for allowing coordinated interactions between neurons and glia. We deleted the gene for one such factor, SOX9, early during mouse brain development and observed a significantly compromised dentate gyrus (DG). We dissected the origin of the defect, targeting embryonic Sox9 deletion to either the DG neuronal progenitor domain or the adjacent cortical hem (CH). We identified in the latter previously uncharacterized ALDH1L1+ astrocytic progenitors, which form a fimbrial-specific glial scaffold necessary for neuronal progenitor migration toward the developing DG. Our results highlight an early crucial role of SOX9 for DG development through regulation of astroglial potential acquisition in the CH. Moreover, we illustrate how formation of a local network, amidst astrocytic and neuronal progenitors originating from adjacent domains, underlays brain morphogenesis.