Excitatory neurotransmission activates compartmentalized calcium transients in Müller glia without affecting lateral process motility

  1. Joshua M Tworig
  2. Chandler Coate
  3. Marla B Feller  Is a corresponding author
  1. University of California, Berkeley, United States

Abstract

Neural activity has been implicated in the motility and outgrowth of glial cell processes throughout the central nervous system. Here we explore this phenomenon in Müller glia, which are specialized radial astroglia that are the predominant glial type of the vertebrate retina. Müller glia extend fine filopodia-like processes into retinal synaptic layers, in similar fashion to brain astrocytes and radial glia which exhibit perisynaptic processes. Using two-photon volumetric imaging, we found that during the second postnatal week, Müller glial processes were highly dynamic, with rapid extensions and retractions that were mediated by cytoskeletal rearrangements. During this same stage of development, retinal waves led to increases in cytosolic calcium within Müller glial lateral processes and stalks. These comprised distinct calcium compartments, distinguished by variable participation in waves, timing, and sensitivity to an M1 muscarinic acetylcholine receptor antagonist. However, we found that motility of lateral processes was unaffected by the presence of pharmacological agents that enhanced or blocked wave-associated calcium transients. Finally, we found that mice lacking normal cholinergic waves in the first postnatal week also exhibited normal Müller glial process morphology. Hence, outgrowth of Müller glial lateral processes into synaptic layers is determined by factors that are independent of neuronal activity.

Data availability

Source data for all figures is available and is uploaded to a linked Dryad repository as well as directly with this submission.

The following data sets were generated

Article and author information

Author details

  1. Joshua M Tworig

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  2. Chandler Coate

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  3. Marla B Feller

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    mfeller@berkeley.edu
    Competing interests
    Marla B Feller, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9137-5849

Funding

National Science Foundation (DGE 1752814)

  • Joshua M Tworig

National Institutes of Health (R01EY019498)

  • Joshua M Tworig
  • Marla B Feller

National Institutes of Health (R01EY013528)

  • Joshua M Tworig
  • Marla B Feller

National Eye Institute (P30EY003176)

  • Joshua M Tworig
  • Marla B Feller

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 Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the University of California, Berkeley. The protocol was approved by the University of California Animal Care and Use Committee Office for Animal Care and Use (Protocol Number: AUP-2015-10-8080-1).

Copyright

© 2021, Tworig 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

  • 1,115
    views
  • 158
    downloads
  • 7
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Joshua M Tworig
  2. Chandler Coate
  3. Marla B Feller
(2021)
Excitatory neurotransmission activates compartmentalized calcium transients in Müller glia without affecting lateral process motility
eLife 10:e73202.
https://doi.org/10.7554/eLife.73202

Share this article

https://doi.org/10.7554/eLife.73202

Further reading

    1. Neuroscience
    Csaba Dávid, Kristóf Giber ... Laszlo Acsady
    Tools and Resources

    Unsupervised segmentation in biological and non-biological images is only partially resolved. Segmentation either requires arbitrary thresholds or large teaching datasets. Here, we propose a spatial autocorrelation method based on Local Moran’s I coefficient to differentiate signal, background, and noise in any type of image. The method, originally described for geoinformatics, does not require a predefined intensity threshold or teaching algorithm for image segmentation and allows quantitative comparison of samples obtained in different conditions. It utilizes relative intensity as well as spatial information of neighboring elements to select spatially contiguous groups of pixels. We demonstrate that Moran’s method outperforms threshold-based method in both artificially generated as well as in natural images especially when background noise is substantial. This superior performance can be attributed to the exclusion of false positive pixels resulting from isolated, high intensity pixels in high noise conditions. To test the method’s power in real situation, we used high power confocal images of the somatosensory thalamus immunostained for Kv4.2 and Kv4.3 (A-type) voltage-gated potassium channels in mice. Moran’s method identified high-intensity Kv4.2 and Kv4.3 ion channel clusters in the thalamic neuropil. Spatial distribution of these clusters displayed strong correlation with large sensory axon terminals of subcortical origin. The unique association of the special presynaptic terminals and a postsynaptic voltage-gated ion channel cluster was confirmed with electron microscopy. These data demonstrate that Moran’s method is a rapid, simple image segmentation method optimal for variable and high noise conditions.

    1. Neuroscience
    Kelly A Bennion, Jade Phong ... James W Antony
    Research Article

    Over the past century of memory research, the interplay between initial and later-learned information in determining long-term memory retention has been of central interest. A likely factor for determining whether initial and later memories interfere with or strengthen each other is semantic relatedness. Relatedness has been shown to retroactively boost initial memory and increase the interdependence between earlier and more recent experiences in memory. Here, we investigated the converse relationship of how relatedness proactively affects later memory for paired associates. In five experiments (N=1000 total), we varied the relatedness between initial and later cues, initial and later targets, or both. Across experiments and conditions, relatedness profoundly benefited later-learned memories – in some conditions, low relatedness reliably produced proactive interference (versus a control condition) while high relatedness produced proactive facilitation within the same experiment. Additionally, relatedness also accelerated learning and increased interdependence between initial and later-learned pairs. In sum, we demonstrate the robust effects of relatedness in scaffolding memory for recently learned information and creating strong integrative links with prior experiences.