Dopamine-induced hippocampal plasticity: A synaptic model of foraging in mice

记忆对于社会的正常功能和我们作为人类的身份都很重要。许多因素影响我们的记忆力。例如，直觉上，获得奖励有助于你学习。在你学习之后获得奖励也可以帮助你记忆。但是，后来发生的事情怎么会有助于加强对以前发生的事情的记忆呢？这就是我们在这个建议中要解决的难题;我们将研究奖励如何影响对先前经验的记忆的机制。我们可以通过研究老鼠如何学习奖励的位置，然后在稍后的时间使用它们的记忆导航回到同一个地方来研究这一点。为此，我们将使用计算机模型来预测老鼠如何对奖励做出反应，以及它们如何找到奖励的位置。然后，我们将在真实的小鼠中测试这些预测。我们将在一个简单的迷宫中的特定位置给老鼠食物奖励，然后研究它们如何导航到这些奖励的位置。如果我们的计算机预测是正确的，老鼠将使用大脑中被称为海马体的一部分在迷宫的心理地图上标记奖励的位置，然后使用这个地图导航回到这个地方。为了验证这个想法，我们将使用一种称为光遗传学的新技术，用激光激活或沉默小鼠大脑的一部分。然后，我们将测试海马体是否是动物找到奖励所必需的，以及奖励信号是否需要进入海马体才能在心理地图上标记奖励位置。这些结果应该让我们对记忆的工作原理以及动物如何利用它们对奖励位置的记忆进行导航有了新的认识。

Memory is important for normal function in society and for our identity as human beings. Many factors influence how well we remember. For example, intuitively, receiving a reward helps you to learn. Receiving a reward after you have learnt can also help you remember. But how is it that later events can help strengthen memories for what happened earlier? This is the conundrum we will address in this proposal; we will study the mechanisms for how reward influences memory of preceding experience. We can investigate this in mice by studying how they learn the location of a reward and then use their memory to navigate back to that same place at a later time. To this end, we will use computer models to predict how mice respond to rewards, and how they find rewarded locations. Then, we will test these predictions in real mice. We will give the mice a food reward at specific locations in a simple maze and then study how they navigate to these rewarded locations. If our computer prediction is correct, the mice will use a part of the brain known as the hippocampus to mark the rewarded locations on a mental map of the maze and then use this map to navigate back to this place. To test this idea, we will use a new technique known as optogenetics to activate or silence part of the mouse brain using a laser. We will then test whether the hippocampus is necessary for the animals to find the rewards, and whether a reward signal needs to enter the hippocampus to mark the reward locations on the mental map. The results should give us new insights into how memory works and how animals navigate using their memory of rewarded locations.