Lardi-Studler Barbara, Fritschy Jean-Marc
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Neuroscientist. 2007 Apr;13(2):115-26. doi: 10.1177/1073858406296803.
Formation of chemical synapses in the central nervous system is a highly regulated, multistep process that requires bidirectional communication across the synaptic cleft. Neurotransmitter receptors, scaffolding proteins, and signaling molecules need to be concentrated in the postsynaptic density, a specialized membrane microdomain apposed to the active zone of presynaptic terminals, where transmitter release occurs. This precise, synapse-specific matching implicates that sorting and targeting mechanisms exist for the molecular constituents of different types of synapses to ensure correct formation of neuronal circuits in the brain. There is considerable evidence from in vitro and in vivo studies that neurotransmitter signaling is not required for proper sorting during synapse formation, whereas active neurotransmission is essential for long-term synapse maintenance. Here, the authors review recent studies on the role of cell adhesion molecules in synaptogenesis and on possible mechanisms ensuring correct matching of pre- and postsynaptic sites. They discuss the role of neurotransmitter receptors and scaffolding proteins in these processes, focusing on fundamental differences between synapse formation during development and synapse maintenance and plasticity in adulthood.
中枢神经系统中化学突触的形成是一个高度受调控的多步骤过程，需要跨突触间隙进行双向通信。神经递质受体、支架蛋白和信号分子需要集中在突触后致密区，这是一个与突触前终末活性区相对的特殊膜微区，神经递质在此处释放。这种精确的、突触特异性的匹配意味着存在针对不同类型突触分子成分的分选和靶向机制，以确保大脑中神经回路的正确形成。体外和体内研究有大量证据表明，神经递质信号在突触形成过程中的正确分选并非必需，而活跃的神经传递对于突触的长期维持至关重要。在此，作者综述了关于细胞黏附分子在突触发生中的作用以及确保突触前和突触后位点正确匹配的可能机制的近期研究。他们讨论了神经递质受体和支架蛋白在这些过程中的作用，重点关注发育过程中突触形成与成年期突触维持和可塑性之间的根本差异。
