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The inhibitory microcircuit of the substantia nigra provides feedback gain control of the basal ganglia output

  1. Jennifer Brown
  2. Wei-Xing Pan
  3. Joshua T Dudman  Is a corresponding author
  1. Janelia Farm Research Campus, Howard Hughes Medical Institute, United States
Research Article
  • Cited 11
  • Views 2,873
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Cite this article as: eLife 2014;3:e02397 doi: 10.7554/eLife.02397

Abstract

Dysfunction of the basal ganglia produces severe deficits in the timing, initiation, and vigor of movement. These diverse impairments suggest a control system gone awry. In engineered systems feedback is critical for control. By contrast, models of the basal ganglia highlight feedforward circuitry and ignore intrinsic feedback circuits. Here we show that feedback via axon collaterals of substantia nigra projection neurons control the gain of the basal ganglia output. Through a combination of physiology, optogenetics, anatomy and circuit mapping we elaborate a general circuit mechanism for gain control in a microcircuit lacking interneurons. Our data suggest that diverse tonic firing rates, weak unitary connections and a spatially diffuse collateral circuit with distinct topography and kinetics from feedforward input is sufficient to implement divisive feedback inhibition. The importance of feedback for engineered systems implies that the intranigral microcircuit, despite its absence from canonical models, could be essential to basal ganglia function.

Article and author information

Author details

  1. Jennifer Brown

    Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Wei-Xing Pan

    Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Joshua T Dudman

    Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    For correspondence
    dudmanj@janelia.hhmi.org
    Competing interests
    The authors declare that no competing interests exist.

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 (#08-36, 11-69) of the Janelia Farm Research Campus. The animal care and use program at Janelia Farm Research Campus is accredited by The Association for Assessment and Accreditation of Laboratory Animal Care, International (AAALACi).

Reviewing Editor

  1. Sacha B Nelson, Brandeis University, United States

Publication history

  1. Received: January 26, 2014
  2. Accepted: May 17, 2014
  3. Accepted Manuscript published: May 21, 2014 (version 1)
  4. Version of Record published: June 24, 2014 (version 2)

Copyright

© 2014, Brown 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.

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