Roles of neurotransmitter in synapse formation: Development of neuromuscular junctions lacking choline acetyltransferase

被引:250
作者
Misgeld, T [1 ]
Burgess, RW [1 ]
Lewis, RM [1 ]
Cunningham, JM [1 ]
Lichtman, JW [1 ]
Sanes, JR [1 ]
机构
[1] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S0896-6273(02)01020-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Activity-dependent and -independent signals collaborate to regulate synaptogenesis, but their relative contributions are unclear. Here, we describe the formation of neuromuscular synapses at which neurotransmission is completely and specifically blocked by mutation of the neurotransmitter-synthesizing enzyme choline acetyltransferase. Nerve terminals differentiate extensively in the absence of neurotransmitter, but neurotransmission plays multiple roles in synaptic differentiation. These include influences on the numbers of pre- and postsynaptic partners, the distribution of synapses in the target field, the number of synaptic sites per target cell, and the number of axons per synaptic site. Neurotransmission also regulates the formation or stability of transient acetylcholine receptor-rich processes (myopodia) that may initiate nerve-muscle contact. At subsequent stages, neurotransmission delays some steps in synaptic maturation but accelerates others. Thus, neurotransmission affects synaptogenesis from early stages and coordinates rather than drives synaptic maturation.
引用
收藏
页码:635 / 648
页数:14
相关论文
共 78 条
[1]   Rapid and reversible effects of activity on acetylcholine receptor density at the neuromuscular junction in vivo [J].
Akaaboune, M ;
Culican, SM ;
Turney, SG ;
Lichtman, JW .
SCIENCE, 1999, 286 (5439) :503-507
[2]  
Banks GB, 2001, J COMP NEUROL, V429, P156, DOI 10.1002/1096-9861(20000101)429:1<156::AID-CNE12>3.0.CO
[3]  
2-3
[4]   FORMATION OF SYNAPSES IN STRIATED-MUSCLE DURING DEVELOPMENT [J].
BENNETT, MR ;
PETTIGREW, AG .
JOURNAL OF PHYSIOLOGY-LONDON, 1974, 241 (02) :515-+
[5]  
BETZ H, 1980, J PHYSIOL-LONDON, V302, P197
[6]   ACTIVITY-DEPENDENT DEVELOPMENT OF THE NEUROMUSCULAR SYNAPSE DURING DROSOPHILA EMBRYOGENESIS [J].
BROADIE, K ;
BATE, M .
NEURON, 1993, 11 (04) :607-619
[7]   MOTOR-NERVE SPROUTING [J].
BROWN, MC ;
HOLLAND, RL ;
HOPKINS, WG .
ANNUAL REVIEW OF NEUROSCIENCE, 1981, 4 :17-42
[8]  
BUNGE RP, 1987, J EXP BIOL, V132, P21
[9]   Alternatively spliced isoforms of nerve- and muscle-derived agrin: Their roles at the neuromuscular junction [J].
Burgess, RW ;
Nguyen, QT ;
Son, YJ ;
Lichtman, JW ;
Sanes, JR .
NEURON, 1999, 23 (01) :33-44
[10]   FUNCTIONAL-ANALYSIS OF CONSERVED HISTIDINES IN CHOLINE-ACETYLTRANSFERASE BY SITE-DIRECTED MUTAGENESIS [J].
CARBINI, LA ;
HERSH, LB .
JOURNAL OF NEUROCHEMISTRY, 1993, 61 (01) :247-253