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，这些神经元中的哪些会参与存储这些信息？所有的神经元都是平等的，还是有些神经元比其他神经元更有可能存储记忆？记忆是否总是牵涉到相同的神经元？或者记忆痕迹(即记忆印记)会随着时间的推移而改变，这样你就可以适当地归档记忆，记住重要的信息，并用新的知识更新印记？这些问题都很难回答。但如果我们不回答这些问题，我们永远无法理解大脑是如何工作的，也无法了解如何治疗与痴呆症、抑郁症和精神分裂症等疾病相关的记忆障碍。在过去的几年里，技术已经发展到了这样的地步，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组。这些神经元被称为印记神经元，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。我们可以激活印记神经元(以唤起记忆的回忆)或使其沉默(以删除记忆)。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，发展得很快，因为我们没有能力同时测量数百个神经元的大脑活动。在这个为期3年的系列实验中，我们将结合捕捉印记神经元和记录小鼠海马区和连接的大脑区域中大量神经元的活动，来翻译印记神经元用来学习、处理和记忆新信息的算法。如果没有横跨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印记神经元的活动。我们早在2000年前就知道睡眠有助于健康的记忆，但我们仍然不知道到底是如何做到的。现在我们已经发现了记忆印记神经元，答案可能触手可及。鉴于你的整个人格和世界观都是大脑储存的许多记忆印记的产物，如果我们要理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.