Local processing in neurites of VGluT3-expressing amacrine cells differentially organizes visual information

  1. Jen-Chun Hsiang
  2. Keith Johnson
  3. Linda Madisen
  4. Hongkui Zeng
  5. Daniel Kerschensteiner  Is a corresponding author
  1. Washington University School of Medicine, United States
  2. Allen Institute for Brain Science, United States

Abstract

Neurons receive synaptic inputs on extensive neurite arbors. How information is organized across arbors and how local processing in neurites contributes to circuit function is mostly unknown. Here, we used two-photon Ca2+ imaging to study visual processing in VGluT3-expressing amacrine cells (VG3‑ACs) in the mouse retina. Contrast preferences (ON vs. OFF) varied across VG3‑AC arbors depending on the laminar position of neurites, with ON responses preferring larger stimuli than OFF responses. Although arbors of neighboring cells overlap extensively, imaging population activity revealed continuous topographic maps of visual space in the VG3‑AC plexus. All VG3‑AC neurites responded strongly to object motion, but remained silent during global image motion. Thus, VG3‑AC arbors limit vertical and lateral integration of contrast and location information, respectively. We propose that this local processing enables the dense VG3‑AC plexus to contribute precise object motion signals to diverse targets without distorting target-specific contrast preferences and spatial receptive fields.

Article and author information

Author details

  1. Jen-Chun Hsiang

    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Keith Johnson

    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Linda Madisen

    Allen Institute for Brain Science, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Hongkui Zeng

    Allen Institute for Brain Science, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0326-5878
  5. Daniel Kerschensteiner

    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, United States
    For correspondence
    kerschensteinerd@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6794-9056

Funding

National Eye Institute (EY023341)

  • Daniel Kerschensteiner

Research to Prevent Blindness

  • Daniel Kerschensteiner

National Eye Institute (EY026978)

  • Daniel Kerschensteiner

National Eye Institute (EY 027411)

  • Daniel Kerschensteiner

McDonnell International Scholars Academy

  • Jen-Chun Hsiang

National Institute of General Medical Sciences (GM008151-32)

  • Keith Johnson

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

Reviewing Editor

  1. Fred Rieke, Howard Hughes Medical Institute, University of Washington, United States

Ethics

Animal experimentation: All procedures in this study were approved by the Institutional Animal Care and Use Committee of Washington University School of Medicine (Protocol # 20170033 and were performed in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Version history

  1. Received: August 16, 2017
  2. Accepted: October 11, 2017
  3. Accepted Manuscript published: October 12, 2017 (version 1)
  4. Version of Record published: October 23, 2017 (version 2)
  5. Version of Record updated: October 26, 2017 (version 3)

Copyright

© 2017, Hsiang 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

  • 2,418
    Page views
  • 386
    Downloads
  • 18
    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. Jen-Chun Hsiang
  2. Keith Johnson
  3. Linda Madisen
  4. Hongkui Zeng
  5. Daniel Kerschensteiner
(2017)
Local processing in neurites of VGluT3-expressing amacrine cells differentially organizes visual information
eLife 6:e31307.
https://doi.org/10.7554/eLife.31307

Share this article

https://doi.org/10.7554/eLife.31307

Further reading

    1. Developmental Biology
    2. Neuroscience
    Tariq Zaman, Daniel Vogt ... Michael R Williams
    Research Article

    The cell-type-specific expression of ligand/receptor and cell-adhesion molecules is a fundamental mechanism through which neurons regulate connectivity. Here, we determine a functional relevance of the long-established mutually exclusive expression of the receptor tyrosine kinase Kit and the trans-membrane protein Kit Ligand by discrete populations of neurons in the mammalian brain. Kit is enriched in molecular layer interneurons (MLIs) of the cerebellar cortex (i.e., stellate and basket cells), while cerebellar Kit Ligand is selectively expressed by a target of their inhibition, Purkinje cells (PCs). By in vivo genetic manipulation spanning embryonic development through adulthood, we demonstrate that PC Kit Ligand and MLI Kit are required for, and capable of driving changes in, the inhibition of PCs. Collectively, these works in mice demonstrate that the Kit Ligand/Kit receptor dyad sustains mammalian central synapse function and suggest a rationale for the affiliation of Kit mutation with neurodevelopmental disorders.

    1. Neuroscience
    Hideo Hagihara, Hirotaka Shoji ... Tsuyoshi Miyakawa
    Research Article

    Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer’s disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.