The role of Ago1 and Ago2 in neuronal development and synaptic plasticty

神经细胞通过称为突触的特殊细胞间连接相互通信。突触可塑性，即突触的加强和减弱，是神经元发育和学习记忆形成的重要特征。被广泛研究的脊椎动物突触可塑性的例子是长时程增强(持续性突触增强)和长期抑制(持续性突触减弱)。突触可塑性的短期事件是由蛋白质修饰介导的，而后来的事件需要在突触合成新的蛋白质。某些信使RNA被运输到突触并在突触上翻译的发现，导致了长期可塑性是通过空间和临时限制的蛋白质合成来实现的概念。然而，导致局部翻译诱导的分子信号通路在很大程度上仍然难以捉摸。*我们的研究计划将探讨NMDA受体激活对突触可塑性过程中局部蛋白质合成的影响。我们将测试调节局部翻译的蛋白质是否受到NMDA受体激活的影响，以及这些局部翻译调节因子是否影响突触长期增强或长期抑制的结果。表征突触可塑性过程中调节的不同信号通路，阐明突触蛋白质合成的控制机制，将极大地提高我们对神经元发育以及学习和记忆的基本机制的认识。

Nerve cells communicate with each other via specialized intercellular junctions known as synapses. Synaptic plasticity, which means the strengthening and weakening of synapses, is an important feature of neuronal development as well as for learning and memory formation. Widely studied examples of vertebrate synaptic plasticity are long-term potentiation (persistent synaptic enhancement) and long-term depression (persistent synaptic weakening). Short-term events in synaptic plasticity are mediated by protein modifications, while later events require the synthesis of new proteins at the synapse. The finding that certain messenger RNAs are transported to and translated at the synapse led to the notion that long-term plasticity is implemented by spatially and temporarily restricted protein synthesis. However, the molecular signaling pathways leading to the induction of local translation remain largely elusive. ******Our research proposal will investigate the effect of NMDA-receptor activation on local protein synthesis during synaptic plasticity. We will test whether proteins that regulate local translation are affected by NMDA-receptor activation, and whether these regulators of local translation affect the outcome of long-term potentiation or long-term depression in synapses. Characterizing the different signaling pathways that are regulated during synaptic plasticity and elucidating the control mechanisms for protein synthesis at the synapse will greatly enhance our knowledge of basic mechanisms underlying neuronal development as well as learning and memory.