1. Neuroscience
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Sensitivity and kinetics of signal transmission at the first visual synapse differentially impact visually-guided behavior

  1. Ignacio Sarria
  2. Johan Pahlberg
  3. Yan Cao
  4. Alexander V Kolesnikov
  5. Vladimir J Kefalov
  6. Alapakkam P Sampath
  7. Kirill A Martemyanov  Is a corresponding author
  1. The Scripps Research Institute, United States
  2. University of California, Los Angeles, United States
  3. Washington University in St.Louis, United States
Research Article
  • Cited 7
  • Views 1,288
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Cite this article as: eLife 2015;4:e06358 doi: 10.7554/eLife.06358

Abstract

In the retina, synaptic transmission between photoreceptors and downstream ON-bipolar neurons (ON-BCs) is mediated by a GPCR pathway, which plays an essential role in vision. However, the mechanisms that control signal transmission at this synapse and its relevance to behavior remain poorly understood. In this study we used a genetic system to titrate the rate of GPCR signaling in ON-BC dendrites by varying the concentration of key RGS proteins and measuring the impact on transmission of signal between photoreceptors and ON-BC neurons using electroretinography and single cell recordings. We found that sensitivity, onset timing, and the maximal amplitude of light-evoked responses in rod- and cone-driven ON-BCs are determined by different RGS concentrations. We further show that changes in RGS concentration differentially impact visually guided-behavior mediated by rod and cone ON pathways. These findings illustrate that neuronal circuit properties can be modulated by adjusting parameters of GPCR-based neurotransmission at individual synapses.

Article and author information

Author details

  1. Ignacio Sarria

    Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Johan Pahlberg

    Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yan Cao

    Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexander V Kolesnikov

    Department of Ophthalmology and Visual Sciences, Washington University in St.Louis, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Vladimir J Kefalov

    Department of Ophthalmology and Visual Sciences, Washington University in St.Louis, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Alapakkam P Sampath

    Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Kirill A Martemyanov

    Department of Neuroscience, The Scripps Research Institute, Jupiter, United States
    For correspondence
    kirill@scripps.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All procedures were carried out in accordance with the National Institute of Health guidelines and were granted formal approval by the Institutional Animal Care and Use Committees of the Scripps Research Institute (IACUC protocol number 14-001), Washington University (IACUC protocol number 20140236), and the University of Southern California (IACUC protocol number 10890).

Reviewing Editor

  1. Jeremy Nathans, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: January 6, 2015
  2. Accepted: April 11, 2015
  3. Accepted Manuscript published: April 16, 2015 (version 1)
  4. Version of Record published: April 29, 2015 (version 2)

Copyright

© 2015, Sarria 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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Further reading

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    Synapses of glutamatergic mossy fibers (MFs) onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC’s large dendritic brush. Using mouse brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate was spontaneous, spike-independent exocytosis from the MF terminal, and its level was dependent on activity of glutamate transporters EAAT1–2. Increasing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission.

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    Transmembrane protein Golden goal (Gogo) interacts with atypical cadherin Flamingo to direct R8 photoreceptor axons in the Drosophila visual system. However, the precise mechanisms underlying Gogo regulation during columnar- and layer-specific R8 axon targeting are unknown. Our studies demonstrated that the insulin secreted from surface and cortex glia switches the phosphorylation status of Gogo, thereby regulating its two distinct functions. Non-phosphorylated Gogo mediates the initial recognition of the glial protrusion in the center of the medulla column, whereas phosphorylated Gogo suppresses radial filopodia extension by counteracting Flamingo to maintain a one axon to one column ratio. Later, Gogo expression ceases during the midpupal stage, thus allowing R8 filopodia to extend vertically into the M3 layer. These results demonstrate that the long- and short-range signaling between the glia and R8 axon growth cones regulates growth cone dynamics in a stepwise manner, and thus shape the entire organization of the visual system.