The cover story of the May 4th issue of Neuron reported the ION finding “Activity-induced rapid synaptic maturation mediated by presynaptic cdc42 signaling”. This work was done by graduate students Wan-hua Shen and Bei Wu from the Laboratory of Synapse Development and Plasticity, under the supervision of Dr. Shu-min Duan.

This report is an important breakthrough in understanding the development and maturation of synapses, the key neuronal structure that transmits signals from one nerve cell to another. In the nervous system, the neuron, or nerve cell, is the fundamental unit that functions by conducting electrical and chemical signals throughout the brain. These signals are transmitted between neurons across structures known as synapses. Previously, scientists have observed silent synapses, which have the ultrastructure of synapses but cannot spread signals from one neuron to another. Under certain circumstances, these nonfunctional synapses can be converted into functional ones. It is generally believed that this conversion is important for synapse maturation and may be the basis for processes such as learning and memory. The mechanism underlying unsilencing of synapses has been of great interest to the neuroscience community. According to the classic interpretation, silent synapses are post-synaptically silent, that is, they contain NMPA receptors but lack AMPA receptors; these synapses become unsilenced when stimulations induce insertion of AMPA receptors into the post-synaptic membrane. Dr. Duan and colleagues found another type of silent synapses that have AMPA receptors, but cannot mediate synaptic transmission because the pre-synaptic boutons cannot release the excitatory neurotransmitter glutamate. Activation of pre-synaptic function can be achieved rapidly upon electrical stimulation, transforming the "silent synapses" into functional ones. Further work reveals that the transformation is through activation of small G-proteins, resulting in increased polymerization of the cytoskeleton at presynaptic terminals. In this way, glutamate is released and the silent synapses are no longer silent. In his comments, Ege T. Kavalali, a neuroscientist from the Center for Basic Neuroscience at the University of Texas Southwestern Medical Center, points out that the work "provides a fresh look at these silent synapses and their switching to active ones," and "brings a clear mechanistic insight to this type of off/on switching, which occurs during early synaptic development contributing to the plasticity of synaptic networks." He notes that "a major strength of this study stems from its ability to bring together several disparate earlier observations... in a single coherent model." Experts believe that this work will exert far-reaching influences on understanding the mechanisms of synapse development and plasticity. This work was supported by grants from the Chinese Academy of Science, the Major State Basic Research Program of China (G200077800) and the National Natural Science Foundation of China (30321002).