Neuronal death and suppression of functional synaptic inputs are well-known regressive events characterizing PNS and CNS development. In the CNS, participation of activity in synapse elimination has been known ever since the pioneering studies of Hubel and Wiesel, but only recently has a Hebb-based mechanism of spike synchrony versus asynchrony received unequivocal experimental support in the visual system. At the neuromuscular junction (NMJ), where synapse elimination was discovered, the specific function of the “timing of activity” was addressed by only one group of studies and did not receive widespread attention. Here we critically review the latest NMJ investigation advocating an “activity-independent” mechanism for synapse elimination and contrast it with an equally recent study demonstrating a key role for spike timing. Finally, we highlight how the striking similarities between the two mentioned studies on spike timing (visual system and NMJ) establish conclusively its role in the development of the nervous system in general.
Balice-GordonRJLichtmanJW. 1994. Long-term synapse loss induced by focal blockade of postsynaptic receptors. Nature372(6506):519–24.
2.
BetzWJCaldwellJHRibchesterRR. 1980. The effects of partial denervation at birth on the development of muscle fibres and motor units in rat lumbrical muscle. J Physiol (Lond)303:265–79.
3.
BiGQPooMM. 1998. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type. J Neurosci18(24):10464–72.
4.
BlissTVLømoT. 1973. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol232(2):331–56.
BrownMCJansenJKSVan EssenDC. 1976. Polyneuronal innervation of skeletal muscle in new-born rats and its elimination during maturation. J Physiol261:387–424.
7.
BuffelliMBurgessRWFengGLobeCGLichtmanJWSanesJR. 2003. Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition. Nature424(6947):430–4.
BuffelliMBusettoGCangianoLCangianoA. 2002. Perinatal switch from synchronous to asynchronous activity of motoneurons: link with synapse elimination. Proc Natl Acad Sci U S A99(20):13200–5.
10.
BusettoGBuffelliMTognanaEBellicoFCangianoA. 2000. Hebbian mechanisms revealed by electrical stimulation at developing rat neuromuscular junctions. J Neurosci20(2):685–95.
11.
CangianoALutzembergerL. 1977. Partial denervation affects both denervated and innervated fibres in mammalian skeletal muscle. Science196:542–5.
12.
CangianoALutzembergerL. 1980. Partial denervation in inactive muscle affects innervated and denervated fibres equally. Nature285:233–5.
13.
CangianoAMagheriniPCPasinoEPellegrinoMRisalitiR. 1984. Interaction of inactivity and nerve breakdown products in the origin of acute denervation changes in rat skeletal muscle. J Physiol355:345–65.
14.
DanYPooMM. 2006. Spike timing-dependent plasticity: from synapse to perception. Physiol Rev86(3):1033–48.
15.
DiamondJMilediR. 1962. A study of fetal and new-born rat muscle fibres. J Physiol162:393–408.
16.
El DanafRNHubermanAD. 2012. Wiring visual circuits, one eye at a time. Nat Neurosci15(2):172–4.
17.
FaveroMBuffelliMCangianoABusettoG. 2010. The timing of impulse activity shapes the process of synaptic competition at the neuromuscular junction. Neuroscience167(2):343–53.
18.
FaveroMBusettoGCangianoA. 2012. Spike timing plays a key role in synapse elimination at the neuromuscular junction. Proc Natl Acad Sci U S A109(25):E1667–75.
19.
GanWBLichtmanJW. 1998. Synaptic segregation at the developing neuromuscular junction. Science282(5393):1508–11.
20.
HebbD. 1949. The organization of behavior. New York, NY: Wiley.
21.
HubelDHWieselTN. 1965. Binocular interactions in striate cortex of kittens reared with artificial squint. J Neurophysiol28:1041–59.
22.
JansenJKFladbyT. 1990. The perinatal reorganization of the innervation of skeletal muscle in mammals. Prog Neurobiol34(1):39–90.
23.
KasthuriNLichtmanJW. 2003. The role of neuronal identity in synaptic competition. Nature424(6947):426–30.
24.
KatzLCShatzCJ. 1996. Synaptic activity and the construction of cortical circuits. Science274(5290):1133–8.
25.
Levi-MontalciniR. 1987. The nerve growth factor 35 years later. Science237(4819):1154–62.
26.
LiebermanEHauertCNowakMA. 2005. Evolutionary dynamics on graphs. Nature433(7023):312–6.
27.
LømoTRosenthalJ. 1972. Control of ACh-sensitivity by muscle activity in the rat. J Physiol221:493–513.
28.
LømoTWestgaardR. 1976. Control of ACh sensitivity in rat muscle fibers. Cold Spring Harb Symp Quant Biol40:263–74.
29.
MageeJCJohnstonD. 1997. A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons. Science275(5297):209–13.
30.
MarkramHLubkeJFrotscherMSakmannB. 1997. Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science275(5297):213–5.
31.
OppenheimRWMilliganCEvon BartheldCS. 2012. Programmed cell death and neurotrophic factors. In: SquireLBergDBloomFdu LacSGhoshASpitzerN, editors. Fundamental neuroscience. 4th edition.New York, NY: Elsevier. p 405–35.
32.
PasinoEBuffelliMArancioOBusettoGSalviatiACangianoA. 1996. Effects of long-term conduction block on membrane properties of reinnervated and normally innervated rat skeletal muscle. J Physiol (Lond)497(Pt 2):457–72.
33.
PersoniusKEChangQMentisGZO’DonovanMJBalice-GordonRJ. 2007. Reduced gap junctional coupling leads to uncorrelated motor neuron firing and precocious neuromuscular synapse elimination. Proc Natl Acad Sci U S A104(28):11808–13.
34.
StentGS. 1973. A physiological mechanism for Hebb’s postulate of learning. Proc Natl Acad Sci U S A70(4):997–1001.
35.
StrykerMPStricklandSL. 1984. Physiological segregation of ocular dominance columns depends on the pattern of afferent electrical activity. Invest Ophthalmol Vis Sci25(Suppl.):278.
36.
TapiaJCLichtmanJW. 2012. Synapse elimination. In: SquireLBergDBloomFdu LacSGhoshASpitzerN, editors. Fundamental neuroscience. 4th edition.New York, NY: Elsevier. p 437–55.
37.
ThompsonWJ. 1983. Synapse elimination in neonatal rat muscle is sensitive to the pattern of muscle use. Nature302:614–6.
38.
TurneySGLichtmanJW. 2012. Reversing the outcome of synapse elimination at developing neuromuscular junctions in vivo: evidence for synaptic competition and its mechanism. PLoS Biol10(6):e1001352.
39.
WalshMKLichtmanJW. 2003. In vivo time-lapse imaging of synaptic takeover associated with naturally occurring synapse elimination. Neuron37(1):67–73.
40.
WieselTNHubelDH. 1963. Single-cell responses in striate cortex of kittens deprived of vision in one eye. J Neurophysiol26:1003–17.
41.
ZhangJAckmanJBXuHPCrairMC. 2012. Visual map development depends on the temporal pattern of binocular activity in mice. Nat Neurosci15(2):298–307.
