Role of dopamine in hippocampal plasticity and hippocampus-dependent memory

大脑是如何存储记忆的，这是神经科学中的一大谜团。我们怎么才能回忆起过去发生的事情呢？科学家认为，记忆储存在大脑中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。虽然突触的可塑性可以解释信息的即时存储，但人们对不同记忆是如何联系在一起的了解较少。我们最近发现了一种突触可塑性的机制，可以解释这种联系随着时间的推移，时间尺度为许多分钟。我们已经发现，如果存在特定的信号分子多巴胺，突触的活动会留下痕迹，稍后可以通过突触的接收神经元的活动转变为突触的变化。当我们收到意想不到的奖励时，多巴胺就会释放出来。这一机制可以将我们在奖励之前采取的行动与其奖励结果联系在一起，从而使我们更有可能在未来采取同样的行动再次获得奖励。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，这种释放是否对新记忆的形成是必要的，以及多巴胺是否可以将记忆联系在一起。这些实验将在小鼠大脑中一个已知对记忆很重要的结构--海马体中进行。我们将测试这一假设，即多巴胺的释放对于神经元活动将初始记忆痕迹转换为长期记忆既是必要的，也是充分的。这些实验的结果对于我们理解记忆是如何联系在一起的将是重要的。这些实验将给我们对记忆的新见解，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.