Causal assessment of bilateral CA3-CA1 communication in hippocampal content representation

“你看，在这一刻，一切对我来说都很清楚。但之前发生了什么？这就是我担心的。就像从梦中醒来；我只是不记得了。”上面这句话出自亨利·莫莱森（Henry Molaison， H.M.），他通过手术切除了一部分大脑来治疗癫痫。h.m.和其他像他一样的人告诉我们，大脑中有一个叫做海马体的区域及其周围区域，对事件和地点的记忆形成至关重要。为了了解海马体和周围区域如何处理记忆，研究人员转向动物，特别是啮齿动物。人和啮齿类动物的海马体中的神经细胞都表现为“位置细胞”；当受试者处于特定位置时，神经细胞会优先活跃。这些细胞作为一个群体一起行动，可能会为大脑提供周围环境的表征，用于指导空间中的行为。海马体位置细胞也可以对特定的物品、气味或声音做出反应，从而改变它们的活动。这些变化可能会让大脑将离散的位置与特定的信息联系起来，比如奖励或惩罚。我们项目的目的是了解位置细胞如何获取有关奖励在哪里的信息。当老鼠学会在不同的圈地中定位奖励时，我们将从两个脑半球的海马体中进行记录。此外，在学习过程中，我们会通过暂时停止海马体回路两个部分之间的交流来干扰学习。这将使我们能够准确地确定海马体中与学习相关的变化发生的位置。在项目的最后一部分，我们将研究睡眠在稳定记忆中的作用。在清醒时观察到的某些神经元活动模式在睡眠时被重新激活，可能是为了稳定相关的记忆。我们将通过在睡眠中干扰海马神经元之间的交流来验证这一假设，并测试这种干扰对记忆稳定的影响。我们的工作将进一步加深我们对海马体如何将信息结合在一起形成记忆，以及这些记忆如何在睡眠中稳定下来的理解。反过来，这将有助于提高健康个体和记忆相关疾病患者的学习和记忆能力。特别是，睡眠障碍与记忆障碍有关，与睡眠相关的干预措施似乎有所帮助。确切地了解睡眠如何促进记忆稳定将使我们能够改进和优化与睡眠相关的干预措施。此外，这项工作应该揭示大脑回路用于优化学习的策略，这可以为模仿大脑的行为以实现有效的机器学习提供信息。

"You see at this moment, everything looks clear to me. But what happened just before? That's what worries me. It's like waking from a dream; I just don't remember." The quote above is from Henry Molaison (H.M.), a patient who had part of his brain surgically removed to cure his epilepsy. H.M., and others like him, taught us that a region of the brain called the hippocampus, and surrounding regions, are crucial for the formation of memories of events and places. In order to understand how the hippocampus and surrounding regions process memories, researchers have turned to animals, particularly rodents. Nerve cells in both the human and rodent hippocampus behave as 'place cells'; that is nerve cells that are preferentially active when the subject is at a particular location. These cells, acting together as a population, might provide the brain with a representation of the surrounding environment used to guide behaviour in space. Hippocampal place cells can also change their activity in response to particular items, odours or sounds experienced at a particular location. These changes may allow the brain to associate discrete locations with a particular piece of information, such as a reward or punishment.The aim of our project is to understand how place cells can acquire information about where a reward is. We will record from the hippocampus in both hemispheres while mice learn to locate reward in different enclosures. Furthermore, we will interfere with learning by temporarily silencing communication between two parts of the hippocampus circuit during learning. This will allow us to determine exactly where within the hippocampus learning-related changes happen.In the final part of the project, we will look at the role of sleep in stabilizing memories. Certain neuronal activity patterns observed during active waking behaviour are reactivated during sleep, possibly for the purpose of stabilizing related memories. We will test this hypothesis by interfering with the communication between hippocampal neurons during sleep and testing the effect of this interference on memory stabilization.Our work should further our understanding of how the hippocampus binds information together to form memories, and how these memories are stabilized during sleep. This will in turn aid efforts to enhance learning and memory in both healthy individuals and those with memory related disorders. In particular, sleep malfunctions have been linked to memory impairments and sleep related interventions seem to help. Understanding exactly how sleep promotes memory stabilization will allow us to refine and optimize sleep-related interventions. Moreover, this work should reveal strategies used by brain circuits to optimize learning, which could inform efforts to mimic what the brain does to achieve efficient machine learning.