Glia and muscle sculpt neuromuscular arbors by engulfing destabilized synaptic boutons and shed presynaptic debris.
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.
Fuentes-Medel
Yuly
Y
Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Logan
Mary A
MA
Ashley
James
J
Ataman
Bulent
B
Budnik
Vivian
V
Freeman
Marc R
MR
D000818:Animals; D004330:Drosophila / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009132:Muscles / Q000166:cytology* / Q000502:physiology; D009457:Neuroglia / Q000166:cytology* / Q000502:physiology; D009469:Neuromuscular Junction / Q000166:cytology* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission
D029721:Drosophila Proteins; D008565:Membrane Proteins; C495322:drpr protein, Drosophila
Neuron. 2004 Nov 18;44(4):651-61
15541313
Trends Neurosci. 1991 Mar;14(3):104-11
1709534
Curr Biol. 2006 Sep 5;16(17):1741-7
16950113
Neuron. 2006 Jun 15;50(6):883-95
16772170
Neuron. 1996 Oct;17(4):641-54
8893022
Glia. 2000 Apr;30(2):122-33
10719354
Neuron. 2003 May 22;38(4):567-80
12765609
Science. 2006 May 19;312(5776):1051-4
16614170
Neuron. 2003 Jun 19;38(6):871-85
12818174
Prog Neurobiol. 1998 May;55(1):1-26
9602498
Int Rev Neurobiol. 2006;75:237-65
17137931
Genetics. 1999 Mar;151(3):1093-101
10049925
Neuron. 2006 Jun 15;50(6):855-67
16772168
Neuron. 2008 Jul 31;59(2):253-60
18667153
Neuron Glia Biol. 2007 Feb;3(1):63-74
18172512
Neuron. 2006 Jun 1;50(5):723-33
16731511
Neuron. 1999 Mar;22(3):451-61
10197526
Science. 1994 Feb 18;263(5149):977-80
8310297
Prog Brain Res. 2005;147:43-65
15581697
Brain Res. 2007 Oct 31;1178:52-64
17904536
Neuron. 2003 Jan 9;37(1):67-73
12526773
Neuron. 2008 Mar 13;57(5):705-18
18341991
J Neurosci. 1989 Dec;9(12):4318-32
2512376
Neuron. 1996 Oct;17(4):627-40
8893021
Neuron. 2002 Feb 14;33(4):545-58
11856529
J Neurosci. 2006 Mar 22;26(12):3319-29
16554482
Int J Neurosci. 2005 Jun;115(6):803-28
16019575
Z Zellforsch Mikrosk Anat. 1968;85(2):145-57
5706753
J Neurosci. 1990 Nov;10(11):3754-68
1700086
J Neurosci. 1987 Dec;7(12):4137-44
3320283
Annu Rev Neurosci. 2005;28:127-56
16022592
Annu Rev Neurosci. 2007;30:79-97
17280523
J Physiol. 1976 Oct;262(1):189-214
11339
Development. 2000 Oct;127(19):4157-68
10976048
Neuroscientist. 2005 Oct;11(5):503-13
16151050
J Neurosci. 1996 May 15;16(10):3154-65
8627354
Development. 2007 Jan;134(1):105-16
17164416
J Neurobiol. 1993 Aug;24(8):1025-44
8409967
Annu Rev Cell Dev Biol. 2004;20:193-221
15473839
Proc Natl Acad Sci U S A. 1982 Apr;79(8):2700-4
6806816
Curr Biol. 1996 Jun 1;6(6):695-706
8793296
Cell. 1999 Aug 6;98(3):353-63
10458610
Neuron. 1999 Apr;22(4):719-29
10230792
J Neurosci. 1990 Aug;10(8):2660-71
2388082
J Neurosci. 1998 Feb 1;18(3):956-64
9437017
Curr Opin Neurobiol. 2009 Apr;19(2):162-7
19457653
Neuron. 2006 Jun 15;50(6):869-81
16772169
J Neurosci. 1993 Sep;13(9):3692-704
8366341