Ensheathing Glia Function as Phagocytes in the Adult Drosophila Brain

Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605-2324, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 05/2009; 29(15):4768-81. DOI: 10.1523/JNEUROSCI.5951-08.2009
Source: PubMed


The mammalian brain contains many subtypes of glia that vary in their morphologies, gene expression profiles, and functional roles; however, the functional diversity of glia in the adult Drosophila brain remains poorly defined. Here we define the diversity of glial subtypes that exist in the adult Drosophila brain, show they bear striking similarity to mammalian brain glia, and identify the major phagocytic cell type responsible for engulfing degenerating axons after acute axotomy. We find that neuropil regions contain two different populations of glia: ensheathing glia and astrocytes. Ensheathing glia enwrap major structures in the adult brain, but are not closely associated with synapses. Interestingly, we find these glia uniquely express key components of the glial phagocytic machinery (e.g., the engulfment receptor Draper, and dCed-6), respond morphologically to axon injury, and autonomously require components of the Draper signaling pathway for successful clearance of degenerating axons from the injured brain. Astrocytic glia, in contrast, do not express Draper or dCed-6, fail to respond morphologically to axon injury, and appear to play no role in clearance of degenerating axons from the brain. However, astrocytic glia are closely associated with synaptic regions in neuropil, and express excitatory amino acid transporters, which are presumably required for the clearance of excess neurotransmitters at the synaptic cleft. Together these results argue that ensheathing glia and astrocytes are preprogrammed cell types in the adult Drosophila brain, with ensheathing glia acting as phagocytes after axotomy, and astrocytes potentially modulating synapse formation and signaling.

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    • "memory tasks ( Han et al . , 2013 ; Windrem et al . , 2014 ) . This was an important observation , especially because astrocyte morphology and function appear some - what evolutionarily conserved : in Drosophila , astrocytes also form a dense meshwork of processes that wrap around syn - apses and are essential for animal development and survival ( Doherty et al . , 2009 ; Stork et al . , 2014 ) . Such observations suggest a reasonable scope for the extrapolation of astroglial physiology from experimental animals ( mainly rodents ) to humans ."
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    ABSTRACT: Memory formation in the brain is thought to rely on the remodeling of synaptic connections which eventually results in neural network rewiring. This remodeling is likely to involve ultrathin astroglial protrusions which often occur in the immediate vicinity of excitatory synapses. The phenomenology, cellular mechanisms, and causal relationships of such astroglial restructuring remain, however, poorly understood. This is in large part because monitoring and probing of the underpinning molecular machinery on the scale of nanoscopic astroglial compartments remains a challenge. Here we briefly summarize the current knowledge regarding the cellular organisation of astroglia in the synaptic microenvironment and discuss molecular mechanisms potentially involved in use-dependent astroglial morphogenesis. We also discuss recent observations concerning morphological astroglial plasticity, the respective monitoring methods, and some of the newly emerging techniques that might help with conceptual advances in the area. GLIA 2015. © 2015 The Authors. Glia Published by Wiley Periodicals, Inc.
    Glia 03/2015; 63(12). DOI:10.1002/glia.22821 · 6.03 Impact Factor
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    • "Since then, many studies have focused on the distinct function of these two subtypes of glia. It was reported that ensheathing glia expressed engulfment receptors and phagocytosed degenerated axons, and cell death-triggered olfactory circuit plasticity was mediated through ensheathing glia, but astrocyte-like glial cells were not involved in these processes (Doherty et al., 2009; Kazama et al., 2011). In addition, astrocyte-like glia communicated with clock neurons and regulated A B C Fig. 6 "
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    ABSTRACT: Astrocyte-like glial cells are abundant in the central nervous system of adult Drosophila and exhibit morphology similar to astrocytes of mammals. Previous evidence has shown that astrocyte-like glial cells are strongly associated with synapses in the antennal lobe (AL), the first relay of the olfactory system, where olfactory receptor neurons (ORNs) transmit information into projection neurons (PNs). However, the function of astrocyte-like glia in the AL remains obscure. In this study, using in vivo calcium imaging, we found that astrocyte-like glial cells exhibited spontaneous microdomain calcium elevations. Using simultaneous manipulation of glial activity and monitoring of neuronal function, we found that the astrocyte-like glial activation, but not ensheathing glial activation, could inhibit odor-evoked responses of PNs. Ensheathing glial cells are another subtype of glia, and are of functional importance in the AL. Electrophysiological experiments indicated that astrocyte-like glial activation decreased the amplitude and slope of excitatory postsynaptic potentials evoked through electrical stimulation of the antennal nerve. These results suggest that astrocyte-like glial cells may regulate olfactory processing through negative regulation of ORN-PN synaptic strength. Beyond the antennal lobe we observed astrocyte-like glial spontaneous calcium activities in the ventromedial protocerebrum, indicating that astrocyte-like glial spontaneous calcium elevations might be general in the adult fly brain. Overall, our study demonstrates a new function for astrocyte-like glial cells in the physiological modulation of olfactory information transmission, possibly through regulating ORN-PN synapse strength.
    European Journal of Neuroscience 06/2014; 40(5). DOI:10.1111/ejn.12646 · 3.18 Impact Factor
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    • "Previous work has shown that glia play a major role in the clearance of MB γ axon fragments following developmental axon fragmentation [8], [9], however the precise identity of these glia is unknown. In the adult animal, injured olfactory receptor neurons undergoing Wallerian degeneration are engulfed by ensheathing glia [12]. As a first step, we first wished to identify which glia are located in the vicinity of the MB during metamorphosis. "
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    ABSTRACT: Axon pruning is an evolutionarily conserved strategy used to remodel neuronal connections during development. The Drosophila mushroom body (MB) undergoes neuronal remodeling in a highly stereotypical and tightly regulated manner, however many open questions remain. Although it has been previously shown that glia instruct pruning by secreting a TGF-β ligand, myoglianin, which primes MB neurons for fragmentation and also later engulf the axonal debris once fragmentation has been completed, which glia subtypes participate in these processes as well as the molecular details are unknown. Here we show that, unexpectedly, astrocytes are the major glial subtype that is responsible for the clearance of MB axon debris following fragmentation, even though they represent only a minority of glia in the MB area during remodeling. Furthermore, we show that astrocytes both promote fragmentation of MB axons as well as clear axonal debris and that this process is mediated by ecdysone signaling in the astrocytes themselves. In addition, we found that blocking the expression of the cell engulfment receptor Draper in astrocytes only affects axonal debris clearance. Thereby we uncoupled the function of astrocytes in promoting axon fragmentation to that of clearing axonal debris after fragmentation has been completed. Our study finds a novel role for astrocytes in the MB and suggests two separate pathways in which they affect developmental axon pruning.
    PLoS ONE 01/2014; 9(1):e86178. DOI:10.1371/journal.pone.0086178 · 3.23 Impact Factor
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