Dynamics of protein synthesis in dopamine-dependent hippocampal synaptic plasticity

大脑是如何长时间地将我们的经历存储在记忆中的？人们认为记忆是以神经元之间连接的变化（称为突触）的形式存储的。我们认为，当记忆被储存时，神经元之间的联系会变得更强。一个神经元对另一个神经元的反应强度取决于突触上的蛋白质（受体）。为了使记忆持久，细胞需要产生新的蛋白质。然而，我们仍然不清楚哪些信号通知细胞何时应该产生新的蛋白质，我们也不知道蛋白质是如何专门传递给那些应该加强的连接的。在拟议的项目中，我们将首先研究信号如何诱导神经元产生新的蛋白质。在我们每天经历的所有事件中，为什么有些会被记住，而另一些则不会？许多因素可能会影响我们的记忆力。例如，奖励的呈现可以帮助我们更好地记住事件。先前的研究表明，当我们获得奖励时释放的多巴胺是神经元产生新蛋白质所必需的。在这里，我们想研究多巴胺如何向细胞发出信号，使其产生新蛋白质的潜在机制。我们还想研究新产生的蛋白质如何在细胞中分布并传递到特定的连接。为了解决这些问题，我们将使用新的标记技术，使我们能够区分新产生的蛋白质和细胞中已经存在的蛋白质。这些结果应该让我们对记忆是如何储存的有了新的认识，并可能为改善老年人的记忆和治疗记忆障碍开辟新的途径。

How can the brain store our experiences in memory over long time periods? It is thought that memories are stored as changes in the connections between neurons, called synapses. We think that when a memory is stored, the connection between neurons becomes stronger. How strong one neuron responds to another depends on proteins (receptors) that are present at synapses. For memories to become persistent, the cell needs to produce new proteins. However, we still do not understand well which signals inform the cell when new proteins should be made, and we also do not know how the proteins are delivered specifically to those connections that should be strengthened. In the proposed project, we will first study how signals induce neurons to make new proteins. Of all the events that we experience each day, why is it that some are remembered and others not? Many factors may influence how well we remember. For example, the presentation of a reward may help us remember the event better. Previous research has shown that dopamine, which is released when we receive a reward, is necessary for the neurons to produce new proteins. Here we want to study the underlying mechanism of how dopamine signals to the cell that it should make new protein. We also want to study how the newly produced proteins are distributed in the cell and delivered to the specific connections. To address these questions, we will use new labelling techniques that allow us to distinguish newly produced proteins from those that were already present in the cell. The results should give us new insights into how memories are stored and could potentially open up new avenues for improving memory in ageing individuals and for treating memory disorder.