The role of neuronal identity in synaptic competition

In developing mammalian muscle, axon branches of several motor neurons co-innervate the same muscle fibre. Competition among them results in the strengthening of one and the withdrawal of the rest. It is not known why one particular axon branch survives or why some competitions resolve sooner than others. Here we show that the fate of axonal branches is strictly related to the identity of the axons with which they compete. When two neurons co-innervate multiple target cells, the losing axon branches in each contest belong to the same neuron and are at nearly the same stage of withdrawal. The axonal arbor of one neuron engages in multiple sets of competitions simultaneously. Each set proceeds at a different rate and heads towards a common outcome based on the identity of the competitor. Competitive vigour at each of these sets of local competitions depends on a globally distributed resource: neurons with larger arborizations are at a competitive disadvantage when confronting neurons with smaller arborizations. An accompanying paper tests the idea that the amount of neurotransmitter released is this global resource.

[1]  D. V. van Essen,et al.  Polyneuronal innervation of skeletal muscle in new‐born rats and its elimination during maturation. , 1976, The Journal of physiology.

[2]  J. Lichtman.  The reorganization of synaptic connexions in the rat submandibular ganglion during post‐natal development. , 1977, The Journal of physiology.

[3]  D. Purves,et al.  Elimination of synapses in the developing nervous system. , 1980, Science.

[4]  J. Jansen,et al.  The perinatal reorganization of the innervation of skeletal muscle in mammals , 1990, Progress in Neurobiology.

[5]  Jeff W. Lichtman,et al.  Long-term synapse loss induced by focal blockade of postsynaptlc receptors , 1994, Nature.

[6]  J. Lichtman,et al.  Alterations in Synaptic Strength Preceding Axon Withdrawal , 1997, Science.

[7]  J. Lichtman,et al.  Synaptic segregation at the developing neuromuscular junction. , 1998, Science.

[8]  J. Sanes,et al.  Development of the vertebrate neuromuscular junction. , 1999, Annual review of neuroscience.

[9]  Jeff W. Lichtman,et al.  Activity-Driven Synapse Elimination Leads Paradoxically to Domination by Inactive Neurons , 1999, The Journal of Neuroscience.

[10]  G. Feng,et al.  Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFP , 2000, Neuron.

[11]  R. Balice-Gordon,et al.  Activity-dependent editing of neuromuscular synaptic connections , 2000, Brain Research Bulletin.

[12]  W. Regehr,et al.  Developmental Remodeling of the Retinogeniculate Synapse , 2000, Neuron.

[13]  G. Feng,et al.  Asynchronous Synapse Elimination in Neonatal Motor Units Studies Using GFP Transgenic Mice , 2001, Neuron.

[14]  R. Balice-Gordon,et al.  Loss of Correlated Motor Neuron Activity during Synaptic Competition at Developing Neuromuscular Synapses , 2001, Neuron.

[15]  William H. Press,et al.  Numerical recipes in C , 2002 .

[16]  M. Buffelli,et al.  Perinatal switch from synchronous to asynchronous activity of motoneurons: Link with synapse elimination , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[17]  J. Lichtman,et al.  In Vivo Time-Lapse Imaging of Synaptic Takeover Associated with Naturally Occurring Synapse Elimination , 2003, Neuron.

[18]  Karen Zito,et al.  The Flip Side of Synapse Elimination , 2003, Neuron.

[19]  G. Feng,et al.  Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition , 2003, Nature.