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.

Glia Regulate the Development, Function, and Plasticity of the Visual System From Retina to Cortex

“…Here it was shown that calcium activity is compartmentalized in Müller glial stalks (the elongated radial portion of the cell spanning the width of the retina) and processes, with M1 mAChRs mediating calcium events in Müller glial stalks but not in processes (Tworig et al, 2021). Curiously, acute manipulation of retinal wave activity had no effect on lateral process motility in Müller glia, and chronic manipulation had no impact on the distribution, complexity, or length of glial lateral processes, together suggesting a functional decoupling between structural motility and calcium signaling as wave-associated compartmentalized calcium activity was not required for, nor did it regulate Müller glial process motility (Tworig et al, 2021).…”

“…Structurally Müller glia are complex cells with numerous fine filopodial processes extending into the surrounding neural retina which are highly motile throughout development (Tworig et al, 2021 and see review in this Research Topic). Whether calcium activity in glial cells regulates the structural motility of their processes had remained an open question until recently.…”