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Behavioral evidence for feedback gain control by the inhibitory microcircuit of the substantia nigra

Jennifer Brown, Kathleen A. Martin, View ORCID ProfileJoshua T. Dudman
doi: https://doi.org/10.1101/090209
Jennifer Brown
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
2Current address: Department of Molecular and Cell Biology, University of California at Berkeley, CA, USA
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Kathleen A. Martin
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
3Current address: Neuroscience Institute and Neuroscience and Physiology, New York University School of Medicine, New York, NY, USA
4Current address: Center for Neural Science, New York University, New York, NY, USA.
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Joshua T. Dudman
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
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  • ORCID record for Joshua T. Dudman
  • For correspondence: dudmanj@janelia.hhmi.org
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Abstract

We recently demonstrated that the collaterals of substantia nigra (SN) projection neurons can implement divisive feedback inhibition, or gain control (Brown et al., 2014). While in vivo recordings were consistent with divisive feedback inhibition, a causal test was lacking. A gain control model of the nigral microcircuit implies behavioral effects of disrupting intranigral inhibition that are distinct from previous functional models. To test the model predictions experimentally, we develop a chemogenetic approach that can selectively suppress synaptic release within the substantial nigra without affecting the propagation of activity to extranigral targets. We observe behavioral consequences of suppressing intranigral inhibition that are uniquely consistent with a gain control model. Our data further suggest that if endogenous metabotropic signaling can modulate intranigral synapses, this would provide a circuit mechanism for an exploitation/exploration trade-off in which the timing and variability of goal-directed movements are controlled independently of changes in action.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 28, 2016.
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Behavioral evidence for feedback gain control by the inhibitory microcircuit of the substantia nigra
Jennifer Brown, Kathleen A. Martin, Joshua T. Dudman
bioRxiv 090209; doi: https://doi.org/10.1101/090209
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Behavioral evidence for feedback gain control by the inhibitory microcircuit of the substantia nigra
Jennifer Brown, Kathleen A. Martin, Joshua T. Dudman
bioRxiv 090209; doi: https://doi.org/10.1101/090209

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