miR-9 regulates basal ganglia-dependent developmental vocal learning and adult vocal performance in songbirds

  1. Zhimin Shi
  2. Zoe Piccus
  3. Xiaofang Zhang
  4. Huidi Yang
  5. Hannah Jarrell
  6. Yan Ding
  7. Zhaoqian Teng
  8. Ofer Tchernichovski  Is a corresponding author
  9. XiaoChing Li  Is a corresponding author
  1. Louisiana State University School of Medicine, United States
  2. Hunter College, United States

Abstract

miR-9 is an evolutionarily conserved miRNA that is abundantly expressed in Area X, a basal ganglia nucleus required for vocal learning in songbirds. Here, we report that overexpression of miR-9 in Area X of juvenile zebra finches impairs developmental vocal learning, resulting in a song with syllable omission, reduced similarity to the tutor song, and altered acoustic features. miR-9 overexpression in juveniles also leads to more variable song performance in adulthood, and abolishes social context-dependent modulation of song variability. We further show that these behavioral deficits are accompanied by downregulation of FoxP1 and FoxP2, genes known to be associated with language impairments, disruption of dopamine signaling, and widespread changes in expression of genes important in circuit development and functions. These findings demonstrate a vital role for miR-9 in basal ganglia function and vocal communication, suggesting that dysregulation of miR-9 in humans may contribute to language impairments and related neurodevelopmental disorders.

Article and author information

Author details

  1. Zhimin Shi

    Neuroscience Center of Excellence, Louisiana State University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Zoe Piccus

    Neuroscience Center of Excellence, Louisiana State University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Xiaofang Zhang

    Neuroscience Center of Excellence, Louisiana State University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Huidi Yang

    Neuroscience Center of Excellence, Louisiana State University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Hannah Jarrell

    Neuroscience Center of Excellence, Louisiana State University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Yan Ding

    Neuroscience Center of Excellence, Louisiana State University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Zhaoqian Teng

    Neuroscience Center of Excellence, Louisiana State University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Ofer Tchernichovski

    Department of Psychology, Hunter College, New York, United States
    For correspondence
    tchernichovski@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
  9. XiaoChing Li

    Neuroscience Center of Excellence, Louisiana State University School of Medicine, New Orleans, United States
    For correspondence
    xli4@lsuhsc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7544-494X

Funding

National Institute of Mental Health (R01MH105519)

  • XiaoChing Li

National Science Foundation (1258015)

  • XiaoChing Li

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

Reviewing Editor

  1. Stephanie A White, University of California, Los Angeles, United States

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) protocol (#3187) of the LSU School of Medicine.

Version history

  1. Received: May 30, 2017
  2. Accepted: January 17, 2018
  3. Accepted Manuscript published: January 18, 2018 (version 1)
  4. Version of Record published: February 6, 2018 (version 2)
  5. Version of Record updated: February 15, 2018 (version 3)
  6. Version of Record updated: September 19, 2018 (version 4)

Copyright

© 2018, Shi 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

  • 1,602
    views
  • 191
    downloads
  • 14
    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. Zhimin Shi
  2. Zoe Piccus
  3. Xiaofang Zhang
  4. Huidi Yang
  5. Hannah Jarrell
  6. Yan Ding
  7. Zhaoqian Teng
  8. Ofer Tchernichovski
  9. XiaoChing Li
(2018)
miR-9 regulates basal ganglia-dependent developmental vocal learning and adult vocal performance in songbirds
eLife 7:e29087.
https://doi.org/10.7554/eLife.29087

Share this article

https://doi.org/10.7554/eLife.29087

Further reading

    1. Neuroscience
    Ya-Hui Lin, Li-Wen Wang ... Li-An Chu
    Research Article

    Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

    1. Neuroscience
    Amanda Chu, Nicholas T Gordon ... Michael A McDannald
    Research Article

    Pavlovian fear conditioning has been extensively used to study the behavioral and neural basis of defensive systems. In a typical procedure, a cue is paired with foot shock, and subsequent cue presentation elicits freezing, a behavior theoretically linked to predator detection. Studies have since shown a fear conditioned cue can elicit locomotion, a behavior that - in addition to jumping, and rearing - is theoretically linked to imminent or occurring predation. A criticism of studies observing fear conditioned cue-elicited locomotion is that responding is non-associative. We gave rats Pavlovian fear discrimination over a baseline of reward seeking. TTL-triggered cameras captured 5 behavior frames/s around cue presentation. Experiment 1 examined the emergence of danger-specific behaviors over fear acquisition. Experiment 2 examined the expression of danger-specific behaviors in fear extinction. In total, we scored 112,000 frames for nine discrete behavior categories. Temporal ethograms show that during acquisition, a fear conditioned cue suppresses reward seeking and elicits freezing, but also elicits locomotion, jumping, and rearing - all of which are maximal when foot shock is imminent. During extinction, a fear conditioned cue most prominently suppresses reward seeking, and elicits locomotion that is timed to shock delivery. The independent expression of these behaviors in both experiments reveal a fear conditioned cue to orchestrate a temporally organized suite of behaviors.