The inhibitory microcircuit of the substantia nigra provides feedback gain control of the basal ganglia output
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.
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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).
- Sacha B Nelson, Brandeis University, United States
- Received: January 26, 2014
- Accepted: May 17, 2014
- Accepted Manuscript published: May 21, 2014 (version 1)
- Version of Record published: June 24, 2014 (version 2)
© 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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