The role of rapid, local, postsynaptic protein synthesis in learning-related synaptic facilitation in aplysia.
The role of rapid, local, postsynaptic protein synthesis in learning-related synaptic facilitation in aplysia.
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快速、局部、突触后蛋白质合成在海兔学习相关突触促进中的作用。
DOI：
10.1016/j.cub.2007.10.053
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Glanzman,DavidL
中科院分区：
文献类型：
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作者：
Villareal,Greg;Li,Quan;Cai,Diancai;Glanzman,DavidL
哺乳动物大脑中神经元树突具有蛋白质合成能力的发现[1]激发了人们对局部突触后蛋白质合成在学习相关突触可塑性中的潜在作用的兴趣[2]。但目前还不清楚局部突触后蛋白质合成实际上是如何介导哺乳动物的学习和记忆的。因此，我们研究了是否学习无脊椎动物，海洋snailAparasia，涉及当地，突触后蛋白质合成。以前，我们发现，失智症中防御性退缩反射的去适应和敏化[3，4]需要突触后Ca 2+升高、突触后胞吐作用和突触后α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型谷氨酸受体的功能上调[5]。在这里，我们测试了作为失适应和致敏的基础的突触易化是否需要局部的突触后蛋白质合成。我们发现，易化性递质5-羟色胺（5-HT）增强了运动神经元对谷氨酸（感觉神经元递质）的反应，这种增强依赖于快速的蛋白质合成。通过使用从其细胞体中手术分离的单个运动神经突，我们表明5-HT依赖性蛋白质合成发生在局部。最后，通过阻断突触后蛋白质的合成，我们破坏了感觉运动突触的促进作用。通过证明其在一个主要模型无脊椎动物系统中的学习和记忆的基础突触变化中的关键作用，我们的研究表明，局部突触后蛋白质合成对学习的细胞生物学具有根本的重要性。
The discovery that dendrites of neurons in the mammalian brain possess the capacity for protein synthesis [1] stimulated interest in the potential role of local, postsynaptic protein synthesis in learning-related synaptic plasticity [2]. But it remains unclear how local, postsynaptic protein synthesis actually mediates learning and memory in mammals. Accordingly, we examined whether learning in an invertebrate, the marine snailAplysia, involves local, postsynaptic protein synthesis. Previously, we showed that the dishabituation and sensitization of the defensive withdrawal reflex inAplysia[3, 4] require elevated postsynaptic Ca2+, postsynaptic exocytosis, and functional upregulation of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors [5]. Here, we tested whether the synaptic facilitation that underlies dishabituation and sensitization inAplysia[6] requires local, postsynaptic protein synthesis. We found that the facilitatory transmitter, serotonin (5-HT), enhanced the response of the motor neuron to glutamate, the sensory neuron transmitter, and this enhancement depended on rapid protein synthesis. By using individual motor neurites surgically isolated from their cell bodies, we showed that the 5-HT-dependent protein synthesis occurred locally. Finally, by blocking postsynaptic protein synthesis, we disrupted the facilitation of the sensorimotor synapse. By demonstrating its critical role in a synaptic change that underlies learning and memory in a major model invertebrate system, our study suggests that local, postsynaptic protein synthesis is of fundamental importance to the cell biology of learning.