A MOLECULAR SWITCH ACTIVATED BY METABOTROPIC GLUTAMATE RECEPTORS REGULATES INDUCTION OF LONG-TERM POTENTIATION
A MOLECULAR SWITCH ACTIVATED BY METABOTROPIC GLUTAMATE RECEPTORS REGULATES INDUCTION OF LONG-TERM POTENTIATION
复制标题
DOI：
10.1038/368740a0
复制
发表时间：
1994-04-21
期刊：
影响因子：
64.8
通讯作者：
COLLINGRIDGE, GL
中科院分区：
文献类型：
--
作者：
BORTOLOTTO, ZA;BASHIR, ZI;COLLINGRIDGE, GL
对海马体长时程增强(LTP)的药理学研究开始提供对突触可塑性过程的分子理解，这些过程被认为对脊椎动物的学习和记忆至关重要(1)。在海马区的CA1区，在大多数实验条件下(2，3)，N-甲基-D-天冬氨酸(NMDA)亚型谷氨酸受体的突触激活是诱导LTP所必需的。LTP(4，5)的诱导也需要代谢性谷氨酸受体(MGluRs)的突触激活。我们现在证明了mGluRs在诱导LTP中的作用与NMDA受体的作用是根本不同的。NMDA受体启动一个分子事件，每次破伤风发作时都需要触发该事件来诱导LTP。相反，mGluRs激活了一个分子开关，然后在LTP的诱导过程中不需要mGluR刺激。这种mGluR激活的开关是特定于输入的，可以通过一系列低频刺激来关闭。分子开关是LTP的一个新特征，它对我们理解突触可塑性机制具有重要意义。
PHARMACOLOGICAL studies of long-term potentiation (LTP) in the hippocampus are starting to provide a molecular understanding of synaptic plastic processes which are believed to be important for learning and memory in vertebrates(1). In the CA1 region of the hippocampus, the synaptic activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype is necessary for the induction of LTP under most experimental conditions(2,3). The synaptic activation of metabotropic glutamate receptors (mGluRs) is also needed for the induction of LTP(4,5). We now show that the role of mGluRs in the induction of LTP is fundamentally different from that of NMDA receptors. NMDA receptors initiate a molecular event that needs to be triggered each time a tetanus is delivered to induce LTP. In contrast, mGluRs activate a molecular switch which then negates the need for mGluR stimulation during the induction of LTP. This mGluR-activated switch is input-specific and can be turned off by a train of low-frequency stimulation. The molecular switch is a new feature of LTP which has fundamental consequences for our understanding of synaptic plastic mechanisms.