Excitatory neurotransmission activates compartmentalized calcium transients in Müller glia without affecting lateral process motility
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Curated by eLife
Evaluation Summary:
Tworig and colleagues use the mouse retina to explore the motility of Muller glial processes during development and during retinal waves that drive intracellular calcium signals in Muller glia. This is an important topic, because astrocytes in the brain have been suggested to move relative to synapses during neuronal activity. By performing careful and rigorous experiments, the authors find Muller glia processes move during development, but are not driven to move by neuronal activity. This is an important finding that will be of interest to diverse groups of readers.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)
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- Neuroscience (eLife)
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 that 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 regions 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.
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Evaluation Summary:
Tworig and colleagues use the mouse retina to explore the motility of Muller glial processes during development and during retinal waves that drive intracellular calcium signals in Muller glia. This is an important topic, because astrocytes in the brain have been suggested to move relative to synapses during neuronal activity. By performing careful and rigorous experiments, the authors find Muller glia processes move during development, but are not driven to move by neuronal activity. This is an important finding that will be of interest to diverse groups of readers.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)
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Joint Public Review:
This study examines the possibility that Muller glia (MG) motility in the developing retina prior to eye opening may be controlled or modulated by retinal waves and neural activity. The authors carefully describe the developmental emergence of dynamic filiopdial remodeling in MG in the IPL over the period spanning eye opening and show there is initially a high rate of remodeling which is gradually replaced by stability following eye opening. They further show that motility can be pharmacologically regulated by cytoskeletal manipulations. Using careful quantitative analysis of calcium transients, they unambiguously reveal that MG calcium transients can be up or downregulated (especially in stalks) by increasing or decreasing waves pharmacologically and that mAChRs likely mediate most of the signaling from neurons to …
Joint Public Review:
This study examines the possibility that Muller glia (MG) motility in the developing retina prior to eye opening may be controlled or modulated by retinal waves and neural activity. The authors carefully describe the developmental emergence of dynamic filiopdial remodeling in MG in the IPL over the period spanning eye opening and show there is initially a high rate of remodeling which is gradually replaced by stability following eye opening. They further show that motility can be pharmacologically regulated by cytoskeletal manipulations. Using careful quantitative analysis of calcium transients, they unambiguously reveal that MG calcium transients can be up or downregulated (especially in stalks) by increasing or decreasing waves pharmacologically and that mAChRs likely mediate most of the signaling from neurons to glia underlying this regulation. Finally they perform experiments to alter retinal waves and neuronal activity to test for changes in glial stability. Somewhat surprisingly glial motility was not significantly regulated by retinal neuronal activity. Thus the authors conclude that glial motility in the retina may be independent of calcium transients and neuronal activity. Overall this is a very well designed and technically impressive study. The text is also extremely clear and a pleasure to read. One criticism concerns the underpowered analysis for the morphological dynamics under conditions of neuronal activity blockade.
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