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

多巴胺诱导的海马可塑性：小鼠觅食的突触模型

• 批准号: BB/P019560/1
• 负责人: Ole Paulsen
• 金额: $ 53.73万
• 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: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP019560%2F1
• 关键词: Dopamine; induced; hippocampal; plasticity; synaptic

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.

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。很多因素影响我们的记忆力。例如，从直觉上看，获得奖励有助于你学习。在你学习后获得奖励也能帮助你记忆。但是，后来发生的事情是如何帮助加强对之前发生的事情的记忆的呢？这是我们将在本提案中解决的难题；我们将研究奖励如何影响先前经验记忆的机制。我们可以在老鼠身上研究这一点，通过研究它们是如何学习奖励的位置，然后在稍后的时间里利用它们的记忆导航到同一个地方。为此，我们将使用计算机模型来预测老鼠对奖励的反应，以及它们如何找到奖励地点。然后，我们将在真实的老鼠身上测试这些预测。我们将在一个简单的迷宫的特定地点给老鼠食物奖励，然后研究它们是如何导航到这些奖励地点的。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部分在迷宫的心理地图上标记出奖励的位置，然后使用这张地图导航回到这个地方。为了验证这个想法，我们将使用一种被称为光遗传学的新技术，用激光激活或沉默老鼠大脑的一部分。然后，我们将测试海马体是否对动物找到奖励是必要的，以及奖励信号是否需要进入海马体以在心理地图上标记奖励位置。研究结果将为我们提供新的见解，让我们了解记忆是如何工作的，以及动物是如何利用对奖励地点的记忆进行导航的。

项目成果

Sequential neuromodulation of Hebbian plasticity offers mechanism for effective reward-based navigation

赫布可塑性的顺序神经调节提供了有效的基于奖励的导航机制

• DOI: 10.17863/cam.11354
• 发表时间: 2017
• 作者: Brzosko Z

The functional role of sequentially neuromodulated synaptic plasticity in behavioural learning.

• DOI: 10.1371/journal.pcbi.1009017
• 发表时间: 2021-06
• 期刊: PLoS computational biology
• 影响因子: 4.3
• 作者: Ang GWY;Tang CS;Hay YA;Zannone S;Paulsen O;Clopath C
• 通讯作者: Clopath C

Postsynaptic burst reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs.

海马神经元的突触后爆发重新激活使时间不连续输入的关联可塑性。

• DOI: 10.7554/elife.81071
• 发表时间: 2022-10-13
• 期刊: eLife
• 影响因子: 7.7
• 作者: Fuchsberger T;Clopath C;Jarzebowski P;Brzosko Z;Wang H;Paulsen O
• 通讯作者: Paulsen O

Modulation of hippocampal plasticity in learning and memory

• DOI: 10.1016/j.conb.2022.102558
• 发表时间: 2022-06-02
• 期刊: CURRENT OPINION IN NEUROBIOLOGY
• 影响因子: 5.7
• 作者: Fuchsberger, Tanja;Paulsen, Ole
• 通讯作者: Paulsen, Ole

Postsynaptic burst reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs

海马神经元的突触后爆发重新激活使时间上不连续的输入具有联想可塑性

• DOI: 10.1101/2022.06.23.497305
• 发表时间: 2022
• 作者: Fuchsberger T