Excitatory neurotransmission activates compartmentalized calcium transients in Müller glia without affecting lateral process motility
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.
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Data from: Excitatory neurotransmission activates compartmentalized calcium transients in Müller glia without affecting lateral process motilityDryad Digital Repository, doi:10.6078/d12d9f.
Article and author information
Author details
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.
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