1. Neuroscience

Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells

  1. Loïs S Miraucourt
  2. Jennifer Tsui
  3. Delphine Gobert
  4. Jean-François Desjardins
  5. Anne Schohl
  6. Mari Sild
  7. Perry Spratt
  8. Annie Castonguay
  9. Yves De Koninck
  10. Nicholas Marsh-Armstrong
  11. Paul W Wiseman
  12. Edward S Ruthazer  Is a corresponding author
  1. McGill University, Canada
  2. Institut universitaire en santé mentale de Québec, Canada
  3. Johns Hopkins University School of Medicine, United States
  4. University of La Verne, United States
https://doi.org/10.7554/eLife.15932
Share this article
Cite this article
  1. Loïs S Miraucourt
  2. Jennifer Tsui
  3. Delphine Gobert
  4. Jean-François Desjardins
  5. Anne Schohl
  6. Mari Sild
  7. Perry Spratt
  8. Annie Castonguay
  9. Yves De Koninck
  10. Nicholas Marsh-Armstrong
  11. Paul W Wiseman
  12. Edward S Ruthazer
(2016)
Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells
eLife 5:e15932.
https://doi.org/10.7554/eLife.15932
  2. Download BibTeX
  3. Download .RIS

Abstract

Type 1 cannabinoid receptors (CB1Rs) are widely expressed in the vertebrate retina but the role of endocannabinoids in vision is not fully understood. Here we identified a novel mechanism underlying a CB1R-mediated increase in retinal ganglion cell (RGC) intrinsic excitability acting through AMPK-dependent inhibition of NKCC1 activity. Clomeleon imaging and patch clamp recordings revealed that inhibition of NKCC1 downstream of CB1R activation reduces intracellular Cl- levels in RGCs, hyperpolarizing the resting membrane potential. We confirmed that such hyperpolarization enhances RGC action potential firing in response to subsequent depolarization, consistent with the increased intrinsic excitability of RGCs observed with CB1R activation. Using a dot avoidance assay in freely swimming Xenopus tadpoles we demonstrate that CB1R activation markedly improves visual contrast sensitivity under low light conditions. These results highlight a role for endocannabinoids in vision, and present a novel mechanism for cannabinoid modulation of neuronal activity through Cl- regulation.

Article and author information

Author details

  1. Loïs S Miraucourt

    Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4812-6342

  2. Jennifer Tsui

    Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.

  3. Delphine Gobert

    Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.

  4. Jean-François Desjardins

    Department of Physics, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.

  5. Anne Schohl

    Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.

  6. Mari Sild

    Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.

  7. Perry Spratt

    Montreal Neurological Institute, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.

  8. Annie Castonguay

    Institut universitaire en santé mentale de Québec, Québec, Canada
    Competing interests
    The authors declare that no competing interests exist.

  9. Yves De Koninck

    Institut universitaire en santé mentale de Québec, Québec, Canada
    Competing interests
    The authors declare that no competing interests exist.

  10. Nicholas Marsh-Armstrong

    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Paul W Wiseman

    Department of Biology, University of La Verne, La Verne, United States
    Competing interests
    The authors declare that no competing interests exist.

  12. Edward S Ruthazer

    Montreal Neurological Institute, McGill University, Montreal, Canada
    For correspondence
    edward.ruthazer@mcgill.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0452-3151

Funding

Fonds de Recherche du Québec - Santé (research chair, postdoctoral fellowship)

  • Jennifer Tsui
  • Delphine Gobert
  • Edward S Ruthazer

Canadian Institutes of Health Research (operating grants)

  • Edward S Ruthazer

Epilepsie Canada (postdoctoral award)

  • Loïs S Miraucourt

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Canadian Council on Animal Care. All animals were handled according to animal care committee protocols (#5071) approved by the Animal Care Committees of the Montreal Neurological Institute and McGill University.

Reviewing Editor

  1. Gary L Westbrook, Vollum Institute, United States

Publication history

  1. Received: March 10, 2016
  2. Accepted: August 4, 2016
  3. Accepted Manuscript published: August 8, 2016 (version 1)
  4. Version of Record published: August 16, 2016 (version 2)

Copyright

© 2016, Miraucourt 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

  • 6,243
    Page views
  • 659
    Downloads
  • 11
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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. Loïs S Miraucourt
  2. Jennifer Tsui
  3. Delphine Gobert
  4. Jean-François Desjardins
  5. Anne Schohl
  6. Mari Sild
  7. Perry Spratt
  8. Annie Castonguay
  9. Yves De Koninck
  10. Nicholas Marsh-Armstrong
  11. Paul W Wiseman
  12. Edward S Ruthazer
(2016)
Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells
eLife 5:e15932.
https://doi.org/10.7554/eLife.15932

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Flexible and efficient simulation-based inference for models of decision-making

    Jan Boelts et al.
    Research Advance Updated

    Inferring parameters of computational models that capture experimental data are a central task in cognitive neuroscience. Bayesian statistical inference methods usually require the ability to evaluate the likelihood of the model—however, for many models of interest in cognitive neuroscience, the associated likelihoods cannot be computed efficiently. Simulation-based inference (SBI) offers a solution to this problem by only requiring access to simulations produced by the model. Previously, Fengler et al. introduced likelihood approximation networks (LANs, Fengler et al., 2021) which make it possible to apply SBI to models of decision-making, but require billions of simulations for training. Here, we provide a new SBI method that is substantially more simulation efficient. Our approach, mixed neural likelihood estimation (MNLE), trains neural density estimators on model simulations to emulate the simulator, and is designed to capture both the continuous (e.g., reaction times) and discrete (choices) data of decision-making models. The likelihoods of the emulator can then be used to perform Bayesian parameter inference on experimental data using standard approximate inference methods like Markov Chain Monte Carlo sampling. We demonstrate MNLE on two variants of the drift-diffusion model and show that it is substantially more efficient than LANs: MNLE achieves similar likelihood accuracy with six orders of magnitude fewer training simulations, and is significantly more accurate than LANs when both are trained with the same budget. Our approach enables researchers to perform SBI on custom-tailored models of decision-making, leading to fast iteration of model design for scientific discovery.

    1. Computational and Systems Biology
    2. Neuroscience

    Information flows from hippocampus to auditory cortex during replay of verbal working memory items

    Vasileios Dimakopoulos et al.
    Research Article

    The maintenance of items in working memory (WM) relies on a widespread network of cortical areas and hippocampus where synchronization between electrophysiological recordings reflects functional coupling. We investigated the direction of information flow between auditory cortex and hippocampus while participants heard and then mentally replayed strings of letters in WM by activating their phonological loop. We recorded local field potentials from the hippocampus, reconstructed beamforming sources of scalp EEG, and – additionally in four participants – recorded from subdural cortical electrodes. When analyzing Granger causality, the information flow was from auditory cortex to hippocampus with a peak in the [4 8] Hz range while participants heard the letters. This flow was subsequently reversed during maintenance while participants maintained the letters in memory. The functional interaction between hippocampus and the cortex and the reversal of information flow provide a physiological basis for the encoding of memory items and their active replay during maintenance.

    1. Computational and Systems Biology
    2. Neuroscience

    Parallel processing, hierarchical transformations, and sensorimotor associations along the 'where' pathway

    Raymond Doudlah et al.
    Research Advance

    Visually guided behaviors require the brain to transform ambiguous retinal images into object-level spatial representations and implement sensorimotor transformations. These processes are supported by the dorsal 'where' pathway. However, the specific functional contributions of areas along this pathway remain elusive due in part to methodological differences across studies. We previously showed that macaque caudal intraparietal (CIP) area neurons possess robust three-dimensional (3D) visual representations, carry choice- and saccade-related activity, and exhibit experience-dependent sensorimotor associations (Chang et al., 2020b). Here, we used a common experimental design to reveal parallel processing, hierarchical transformations, and the formation of sensorimotor associations along the 'where' pathway by extending the investigation to V3A, a major feedforward input to CIP. Higher-level 3D representations and choice-related activity were more prevalent in CIP than V3A. Both areas contained saccade-related activity that predicted the direction/timing of eye movements. Intriguingly, the time-course of saccade-related activity in CIP aligned with the temporally integrated V3A output. Sensorimotor associations between 3D orientation and saccade direction preferences were stronger in CIP than V3A, and moderated by choice signals in both areas. Together, the results explicate parallel representations, hierarchical transformations, and functional associations of visual and saccade-related signals at a key juncture in the 'where' pathway.