Role of dopamine in hippocampal plasticity and hippocampus-dependent memory

大脑如何储存记忆是神经科学中最大的谜团之一。我们怎样才能回忆起过去发生的事情呢？科学家认为，记忆储存在大脑神经元之间的连接中。这些连接被称为突触，这些连接强度的变化被称为突触可塑性。尽管突触可塑性可以解释信息的即时存储，但人们对不同的记忆是如何联系在一起的却知之甚少。我们最近发现了一种突触可塑性的机制，可以解释这种随时间推移的联系，时间尺度是几分钟。我们发现，如果存在特定的信号分子多巴胺，那么突触的活动会留下痕迹，这些痕迹可以通过突触的接收神经元的活动转化为突触的变化。当我们得到意想不到的奖励时，多巴胺就会释放出来。这种机制可以将我们在获得奖励之前所采取的行动与奖励结果联系起来，从而使我们更有可能在未来采取同样的行动来获得奖励。现在我们想了解自然释放的多巴胺是如何影响突触可塑性的，这种释放对于新记忆的形成是否必要，以及多巴胺是否可以将记忆联系在一起。实验将在老鼠大脑中一个已知对记忆很重要的结构，即海马体中进行。我们将测试多巴胺的释放是神经元活动将初始记忆痕迹转化为长期记忆的必要和充分的假设。这些实验的结果将对我们理解记忆是如何联系在一起的很重要。这些实验将为我们提供关于记忆的新见解，并可能为提高我们的记忆能力和治疗记忆障碍开辟新的途径。

How the brain stores memories is one of the great mysteries in neuroscience. How can we recollect what happened in the past? Scientists believe that memories are stored in the connections between neurons in the brain. These connections are called synapses, and a change in the strength of these connections is known as synaptic plasticity. Whereas synaptic plasticity can account for the immediate storage of information, it is less well understood how different memories are bound together. We have recently discovered a mechanism of synaptic plasticity that can account for such associations over time, with a time scale of many minutes. We have found that activity at a synapse leaves a trace which can be turned into synaptic changes later by activity of the receiver neuron of the synapse if a specific signalling molecule, dopamine, is present. Dopamine is released when we receive an unexpected reward. This mechanism could link together the actions we took prior to the reward with their rewarding outcome, thus making it more likely that we will take the same actions to be rewarded again in the future. Now we want to understand how naturally released dopamine influences synaptic plasticity, whether such release is necessary for new memories to form, and whether dopamine can link memories together. The experiments will be done in a structure in the mouse brain that is known to be important for memory, namely the hippocampus. We will test the hypothesis that release of dopamine is both necessary and sufficient for neuronal activity to convert an initial memory trace into long-term memory. The results of these experiments will be important for our understanding of how memories are linked together. The experiments will give us new insights into memory and could potentially open new avenues for improving our capacity for memory and for treating memory disorder.