Role of dopamine in hippocampal plasticity and hippocampus-dependent memory

多巴胺在海马可塑性和海马依赖性记忆中的作用

• 批准号: BB/X006557/1
• 负责人: Ole Paulsen
• 金额: $ 67.41万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX006557%2F1
• 关键词: Role; dopamine; hippocampal; plasticity; hippocampus

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.

大脑如何储存记忆是神经科学中最大的谜团之一。我们怎么能忘记过去发生的事情呢？科学家们认为，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。虽然突触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结合在一起的还不太了解。我们最近发现了一种突触可塑性的机制，可以解释这种随着时间推移的关联，时间尺度为许多分钟。我们已经发现，如果存在一种特定的信号分子多巴胺，那么突触上的活动会留下痕迹，这种痕迹后来可以通过突触的接收神经元的活动转化为突触变化。当我们收到意想不到的奖励时，多巴胺就会释放出来。这种机制可以将我们在奖励之前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再次采取同样的行动获得奖励。现在我们想了解自然释放的多巴胺如何影响突触可塑性，这种释放是否是新记忆形成所必需的，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的一个结构中进行，该结构对记忆很重要，即海马体。我们将检验这样一个假设：多巴胺的释放对于神经元活动将最初的记忆痕迹转化为长期记忆是必要的，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非常重要。这些实验将为我们提供对记忆的新见解，并可能为改善我们的记忆能力和治疗记忆障碍开辟新的途径。