Alterations in Synaptic Strength Preceding Axon Withdrawal

Permanent removal of axonal input to postsynaptic cells helps shape the pattern of neuronal connections in response to experience, but the process is poorly understood. Intracellular recording from newborn and adult mouse muscle fibers temporarily innervated by two axons showed an increasing disparity in the synaptic strengths of the two inputs before one was eliminated. The connection that survived gained strength by increasing the amount of neurotransmitter released (quantal content), whereas the input that was subsequently removed became progressively weaker, because of a reduction in quantal content and a reduction in quantal efficacy associated with reduced postsynaptic receptor density. Once the synaptic strengths of two inputs began to diverge, complete axonal withdrawal of the weaker input occurred within 1 to 2 days. These experiments provide a link between experience-driven changes in synaptic strength and long-term changes in connectivity in the mammalian nervous system.

[1]  D. Elmqvist,et al.  Presynaptic action of hemicholinium at the neuromuscular junction , 1965, The Journal of physiology.

[2]  A. W. Morris,et al.  Heavy Metal Concentration in Coastal Waters , 1972, Nature.

[3]  J. D. Del Castillo,et al.  Spreading activation of end-plate receptors by single transmitter quanta. , 1972, Nature: New biology.

[4]  B Katz,et al.  The binding of acetylcholine to receptors and its removal from the synaptic cleft , 1973, The Journal of physiology.

[5]  S. W. Kuffler,et al.  Post‐synaptic potentiation: interaction between quanta of acetylcholine at the skeletal neuromuscular synapse. , 1975, The Journal of physiology.

[6]  A. R. Martin,et al.  Reduction in acetylcholine sensitivity of axotomized ciliary ganglion cells. , 1976, Journal of Physiology.

[7]  R. F. Mayer,et al.  An electrophysiological and morphological study of the neuromuscular junction in patients with myasthenia gravis , 1976, Experimental Neurology.

[8]  J. Rosenthal,et al.  Reduction of multiaxonal innervation at the neuromuscular junction of the rat during development. , 1977, The Journal of physiology.

[9]  W. Betz,et al.  Effects of innervation on acetylcholine sensitivity of developing muscle in vitro. , 1977, The Journal of physiology.

[10]  Y. Kidokoro Developmental changes of spontaneous synaptic potential properties in the rat neuromuscular contact formed in culture. , 1980, Developmental biology.

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

[12]  J. Bixby Ultrastructural observations on synapse elimination in neonatal rabbit skeletal muscle , 1981, Journal of neurocytology.

[13]  C. Cotman,et al.  Synapse replacement in the nervous system of adult vertebrates. , 1981, Physiological reviews.

[14]  M. Glavinović Synaptic depression in frog neuromuscular junction. , 1987, Journal of neurophysiology.

[15]  C. H. Bailey,et al.  The anatomy of a memory: convergence of results across a diversity of tests , 1988, Trends in Neurosciences.

[16]  W. Betz,et al.  Inhibitory interactions between motoneurone terminals in neonatal rat lumbrical muscle. , 1989, The Journal of physiology.

[17]  M. Rich,et al.  In vivo visualization of pre- and postsynaptic changes during synapse elimination in reinnervated mouse muscle , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[19]  Jeff W. Lichtman,et al.  Gradual loss of synaptic cartels precedes axon withdrawal at developing neuromuscular junctions , 1993, Neuron.

[20]  E. Kandel,et al.  Structural changes accompanying memory storage. , 1993, Annual review of physiology.

[21]  D. Linden,et al.  Cellular mechanisms of long-term depression in the cerebellum , 1993, Current Opinion in Neurobiology.

[22]  J. Lichtman,et al.  In vivo observations of pre- and postsynaptic changes during the transition from multiple to single innervation at developing neuromuscular junctions , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[24]  R. Tsien,et al.  Presynaptic component of long-term potentiation visualized at individual hippocampal synapses. , 1995, Science.

[25]  R. Nicoll,et al.  Contrasting properties of two forms of long-term potentiation in the hippocampus , 1995, Nature.

[26]  J. Lichtman Synapse disassembly at the neuromuscular junction , 1995 .