Glia and muscle sculpt neuromuscular arbors by engulfing destabilized synaptic boutons and shed presynaptic debris

PLoS Biol. 2009 Aug;7(8):e1000184. doi: 10.1371/journal.pbio.1000184. Epub 2009 Aug 25.

Abstract

Synapse remodeling is an extremely dynamic process, often regulated by neural activity. Here we show during activity-dependent synaptic growth at the Drosophila NMJ many immature synaptic boutons fail to form stable postsynaptic contacts, are selectively shed from the parent arbor, and degenerate or disappear from the neuromuscular junction (NMJ). Surprisingly, we also observe the widespread appearance of presynaptically derived "debris" during normal synaptic growth. The shedding of both immature boutons and presynaptic debris is enhanced by high-frequency stimulation of motorneurons, indicating that their formation is modulated by neural activity. Interestingly, we find that glia dynamically invade the NMJ and, working together with muscle cells, phagocytose shed presynaptic material. Suppressing engulfment activity in glia or muscle by disrupting the Draper/Ced-6 pathway results in a dramatic accumulation of presynaptic debris, and synaptic growth in turn is severely compromised. Thus actively growing NMJ arbors appear to constitutively generate an excessive number of immature boutons, eliminate those that are not stabilized through a shedding process, and normal synaptic expansion requires the continuous clearance of this material by both glia and muscle cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila / cytology
  • Drosophila / growth & development
  • Drosophila / metabolism
  • Drosophila Proteins / metabolism
  • Larva / cytology
  • Larva / growth & development
  • Larva / metabolism
  • Membrane Proteins / metabolism
  • Microscopy, Confocal
  • Muscles / cytology*
  • Muscles / physiology
  • Neuroglia / cytology*
  • Neuroglia / physiology
  • Neuromuscular Junction / cytology*
  • Neuromuscular Junction / metabolism
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synapses / metabolism
  • Synapses / physiology*
  • Synaptic Transmission

Substances

  • Drosophila Proteins
  • Membrane Proteins
  • drpr protein, Drosophila