A Distinct Perisynaptic Glial Cell Type Forms Tripartite Neuromuscular Synapses in the Drosophila Adult

Abstract

Previous studies of Drosophila flight muscle neuromuscular synapses have revealed their tripartite architecture and established an attractive experimental model for genetic analysis of glial function in synaptic transmission. Here we extend these findings by defining a new Drosophila glial cell type, designated peripheral perisynaptic glia (PPG), which resides in the periphery and interacts specifically with fine motor axon branches forming neuromuscular synapses. Identification and specific labeling of PPG was achieved through cell type-specific RNAi-mediated knockdown (KD) of a glial marker, Glutamine Synthetase 2 (GS2). In addition, comparison among different Drosophila neuromuscular synapse models from adult and larval developmental stages indicated the presence of tripartite synapses on several different muscle types in the adult. In contrast, PPG appear to be absent from larval body wall neuromuscular synapses, which do not exhibit a tripartite architecture but rather are imbedded in the muscle plasma membrane. Evolutionary conservation of tripartite synapse architecture and peripheral perisynaptic glia in vertebrates and Drosophila suggests ancient and conserved roles for glia-synapse interactions in synaptic transmission.

Small heat shock proteins mediate cell-autonomous and -nonautonomous protection in a Drosophila model for environmental-stress-induced degeneration

“…Synaptic regions of the axon also exhibited characteristic contacts with perisynaptic glial processes ( Fig. 2 C,D), as described previously ( Danjo et al, 2011 ; Strauss et al, 2015 ). With regard to muscle, the apparently healthy condition of DLM fibers in no-HS controls was confirmed through visualization of the contractile apparatus by phalloidin staining ( Fig.…”

“…S5B " type="url"/> ), despite severe fragmentation of terminal axon branches. This is in contrast to degeneration of peripheral perisynaptic glia in which both the cell body and glial processes are peripheral ( Strauss et al, 2015 ) and fully degenerated. Finally, axon degeneration does not appear to occur through Wallerian degeneration ( …”

“…2 A-D). These three cell types form DLM neuromuscular synapses, which serve as a model for genetic analysis of molecular mechanisms determining conserved functional properties of synaptic transmission (see Danjo et al, 2011 ; Kawasaki et al, 2011 ; Kawasaki and Ordway, 2009 ; Strauss et al, 2015 ). For studies of DLM neuromuscular synapse morphology, flies were exposed to a standard HS paradigm starting when they were 7 days old and processed for immunocytochemistry at 10 days old (7d HS>10d).…”

“…S9B " type="url"/> ) indicate that these cells are inherently susceptible to both genetic perturbation and environmental stress. Finally, the DLM motor neurons, most of which innervate an entire DLM fiber ( Ikeda and Koenig, 1988 ; Sun and Wyman, 1997 ), and the peripheral perisynaptic glia ( Strauss et al, 2015 ) branch extensively over the entire muscle surface. The large arbors maintained by these cells may, in a manner analogous to those of dopaminergic neurons, contribute to their susceptibility.…”

TRAP-seq Profiling and RNAi-Based Genetic Screens Identify Conserved Glial Genes Required for Adult Drosophila Behavior

“…In both Drosophila and mammals, individual astrocytes have processes that cover a relatively large territory, with the potential to regulate the activities of many different neuronal synapses. Other fly glial types are also components of so-called “tripartite” synapses that regulate neurotransmission (Danjo et al, 2011; Strauss et al, 2015). These features make Drosophila an attractive genetic model for the in vivo analysis of glia-neuron communication.…”