Spatiotemporal properties of glutamate input support direction selectivity in the dendrites of retinal starburst amacrine cells

Abstract

The asymmetric summation of kinetically distinct glutamate inputs across the dendrites of retinal 'starburst' amacrine cells is one of the several mechanisms that have been proposed to underlie their direction-selective properties, but experimentally verifying input kinetics has been a challenge. Here, we used two-photon glutamate sensor (iGluSnFR) imaging to directly measure the input kinetics across individual starburst dendrites. We found that signals measured from proximal dendrites were relatively sustained compared to those measured from distal dendrites. These differences were observed across a range of stimulus sizes and appeared to be shaped mainly by excitatory rather than inhibitory network interactions. Temporal deconvolution analysis suggests that the steady-state vesicle release rate was ~ 3 times larger at proximal sites compared to distal sites. Using a connectomics-inspired computational model, we demonstrate that input kinetics play an important role in shaping direction selectivity at low stimulus velocities. Together, these results provide direct support for the 'space-time wiring' model for direction selectivity.

Data availability

Source data provided

Article and author information

Author details

  1. Prerna Srivastava

    Department of Biology, University of Victoria, Victoria, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Geoff deRosenroll

    Department of Biology, University of Victoria, Victoria, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5431-2814
  3. Akihiro Matsumoto

    Department of Biomedicine, Aarhus University, Aarhus, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  4. Tracy Michaels

    Department of Biology, University of Victoria, Victoria, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Zachary Turple

    Department of Biology, University of Victoria, Victoria, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Varsha Jain

    Department of Biology, University of Victoria, Victoria, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Santhosh Sethuramanujam

    Department of Biology, University of Victoria, Victoria, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Benjamin L Murphy-Baum

    Department of Biology, University of Victoria, Victoria, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6746-3091
  9. Keisuke Yonehara

    Department of Biomedicine, Aarhus University, Aarhus, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  10. Gautam Bhagwan Awatramani

    Department of Biology, University of Victoria, Victoria, Canada
    For correspondence
    gautam@uvic.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0610-5271

Funding

Canadian Institutes of Health Research (159444)

  • Gautam Bhagwan Awatramani

European Research Council (638730)

  • Keisuke Yonehara

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

Reviewing Editor

  1. Marla B Feller, University of California, Berkeley, United States

Ethics

Animal experimentation: All procedures were performed in accordance with the Canadian Council on Animal Care and approved by the University of Victoria's Animal Care Committee, or in accordance with Danish standard ethical guidelines and were approved by the Danish National Animal Experiment Committee (Permission No. 2015-15-0201-00541; 2020-15-0201-00452).

Version history

  1. Received: July 1, 2022
  2. Preprint posted: July 13, 2022 (view preprint)
  3. Accepted: November 2, 2022
  4. Accepted Manuscript published: November 8, 2022 (version 1)
  5. Version of Record published: November 18, 2022 (version 2)

Copyright

© 2022, Srivastava 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

  • 943
    Page views
  • 163
    Downloads
  • 7
    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. Prerna Srivastava
  2. Geoff deRosenroll
  3. Akihiro Matsumoto
  4. Tracy Michaels
  5. Zachary Turple
  6. Varsha Jain
  7. Santhosh Sethuramanujam
  8. Benjamin L Murphy-Baum
  9. Keisuke Yonehara
  10. Gautam Bhagwan Awatramani
(2022)
Spatiotemporal properties of glutamate input support direction selectivity in the dendrites of retinal starburst amacrine cells
eLife 11:e81533.
https://doi.org/10.7554/eLife.81533

Share this article

https://doi.org/10.7554/eLife.81533

Further reading

    1. Neuroscience
    Kiwamu Kudo, Kamalini G Ranasinghe ... Srikantan S Nagarajan
    Research Article

    Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β and misfolded tau proteins causing synaptic dysfunction, and progressive neurodegeneration and cognitive decline. Altered neural oscillations have been consistently demonstrated in AD. However, the trajectories of abnormal neural oscillations in AD progression and their relationship to neurodegeneration and cognitive decline are unknown. Here, we deployed robust event-based sequencing models (EBMs) to investigate the trajectories of long-range and local neural synchrony across AD stages, estimated from resting-state magnetoencephalography. The increases in neural synchrony in the delta-theta band and the decreases in the alpha and beta bands showed progressive changes throughout the stages of the EBM. Decreases in alpha and beta band synchrony preceded both neurodegeneration and cognitive decline, indicating that frequency-specific neuronal synchrony abnormalities are early manifestations of AD pathophysiology. The long-range synchrony effects were greater than the local synchrony, indicating a greater sensitivity of connectivity metrics involving multiple regions of the brain. These results demonstrate the evolution of functional neuronal deficits along the sequence of AD progression.

    1. Medicine
    2. Neuroscience
    Luisa Fassi, Shachar Hochman ... Roi Cohen Kadosh
    Research Article

    In recent years, there has been debate about the effectiveness of treatments from different fields, such as neurostimulation, neurofeedback, brain training, and pharmacotherapy. This debate has been fuelled by contradictory and nuanced experimental findings. Notably, the effectiveness of a given treatment is commonly evaluated by comparing the effect of the active treatment versus the placebo on human health and/or behaviour. However, this approach neglects the individual’s subjective experience of the type of treatment she or he received in establishing treatment efficacy. Here, we show that individual differences in subjective treatment - the thought of receiving the active or placebo condition during an experiment - can explain variability in outcomes better than the actual treatment. We analysed four independent datasets (N = 387 participants), including clinical patients and healthy adults from different age groups who were exposed to different neurostimulation treatments (transcranial magnetic stimulation: Studies 1 and 2; transcranial direct current stimulation: Studies 3 and 4). Our findings show that the inclusion of subjective treatment can provide a better model fit either alone or in interaction with objective treatment (defined as the condition to which participants are assigned in the experiment). These results demonstrate the significant contribution of subjective experience in explaining the variability of clinical, cognitive, and behavioural outcomes. We advocate for existing and future studies in clinical and non-clinical research to start accounting for participants’ subjective beliefs and their interplay with objective treatment when assessing the efficacy of treatments. This approach will be crucial in providing a more accurate estimation of the treatment effect and its source, allowing the development of effective and reproducible interventions.