Memory dynamics: the cellular architecture of systems memory

人类大脑包含大约800亿个神经细胞（神经元）。当你学习新的东西时，哪些神经元会参与存储这些信息？是所有的神经元都是一样的，还是有些神经元比其他神经元更有可能储存记忆？记忆是否总是涉及相同的神经元？或者记忆痕迹（称为“印记”）会随着时间的推移而改变，允许你适当地归档记忆，记住重要信息并用新知识更新印记？这些问题都很难回答。但是，如果我们不回答这些问题，我们就永远无法理解大脑是如何工作的，也永远无法理解如何治疗与痴呆、抑郁和精神分裂症等疾病相关的记忆障碍。在过去几年里，技术已经发展到这样一个程度：我们可以--至少在老鼠身上--“捕捉”参与学习特定记忆的神经元群。这些神经元被称为“记忆痕迹神经元”，最早是在大脑的海马体中发现的，海马体是所有哺乳动物记忆文件的中央索引系统。我们可以激活记忆印记神经元（触发记忆的回忆）或使它们沉默（删除记忆）。在过去的两年里，这些方法改变了我们对记忆机制的理解，但它们是非常新的，而且发展迅速，同时测量数百个神经元的大脑活动的能力也是如此。我们将结合联合收割机对记忆印记神经元的捕获和对小鼠海马和相连脑区中大量神经元活动的记录，来翻译让神经元能够学习、处理和记忆新信息。如果没有来自英国和日本的国际神经科学家团队的参与，这个项目是不可能实现的，他们结合了遗传学，心理学，计算分析和电气工程方面的互补专业知识。我们还将首次测量睡眠期间记忆痕迹神经元的活动。2000年前，我们就知道睡眠有助于健康的记忆，但我们仍然不知道确切的原因。现在我们已经发现了记忆痕迹神经元，答案可能就在眼前，因为你的整个人格和世界观都是大脑存储的许多记忆痕迹的产物，如果我们要了解生命和疾病的基本生物学，这种类型的神经科学仍然是必不可少的。

The human brain contains approximately 80 billion nerve cells (neurons). When you learn something new, which of those neurons will be involved in storing that information? Are all neurons equal, or are some more likely than others to store memories? Will a memory always involve the same neurons? Or will the memory trace (known as an 'engram') change over time, allowing you to file memories appropriately, remembering the important information and updating the engram with new knowledge?These questions are all very challenging to answer. But if we do not answer them, we can never understand how the brain works, or how to treat memory disorders associated with illnesses such as dementia, depression and schizophrenia.Over the past few years, technology has advanced to the point at which we can - at least in mice - "capture" the groups of neurons involved in learning a specific memory. These neurons are known as 'engram neurons', and were first discovered in a part of the brain called the hippocampus, which acts as a central indexing system for memory files in all mammals. We can activate engram neurons (to trigger recall of the memory) or silence them (to delete a memory). These methods have transformed our understanding of memory mechanisms over the past 2 years, but they are very new and evolving rapidly, as is out ability to measure brain activity from hundreds of neurons simultaneously.In this 3-year series of experiments, we will combine capture of engram neurons with recording the activity from large populations of neurons in mouse hippocampus and connected brain regions to translate the algorithms used by engram neurons to learn, process and remember new information. This project would not be possible without the international team of neuroscientists involved, which spans the UK and Japan, uniting complementary expertise in genetics, psychology, computational analyses and electrical engineering.We will also measure, for the first time, the activity of engram neurons during sleep. We have known for 2000 years that sleep supports healthy memory, but we still do not know precisely how. Now we have discovered engram neurons, the answers may be within reach.Given that your entire personality and worldview are products of the many memory engrams stored by your brain, neuroscience of this type remains essential if we are to understand the fundamental biology of life and disease.