Cellular and network dynamics of temporal lobe memory structures

我的实验室研究记忆永久(巩固)背后的神经过程。我们最感兴趣的是情景记忆的子类型，它可以描述为对独特经历的“谁、什么、哪里和何时”方面的回忆。这些记忆依赖于内侧颞叶记忆系统，该系统包括大脑中新皮质和海马体之间广泛的相互联系。这个扩展电路中的神经活动模式不仅对记忆发生时的编码(即在线记忆编码)很重要，而且对事后加强现有记忆(即脱机记忆巩固)也很重要。我们的实验室特别感兴趣的是，在主动学习之后的一段时间内(特别是在慢波活动期间，如睡眠中发生的)，不同的离线自发活动模式如何在记忆巩固中发挥作用。事实证明，学习之后的这段时间对于保持记忆本身是必不可少的。例如，在一次特殊的新奇经历之后，我们知道海马神经元的活动会“重放”实际的序列模式，该模式复制了在实际体验过程中发生的模式。这种重放可能是一种形式的“神经预演”，因为它发生得越多，该特定信息的未来记忆性能实际上就越好(反之亦然--干扰重放会恶化后续的记忆性能)。这可以用“熟能生巧”一句话来概括。大脑进行这种排练的能力似乎也依赖于状态，只有当大脑实际上处于“脱机”状态时才会发生，例如在睡眠期间。因此，研究这一活动是如何发生的，对于理解其在整合中的作用非常重要。我们的后续计划将集中在3个主要目标上：1)利用高密度多部位神经生理学方法以及化学和光遗传学技术，识别和表征内侧颞叶形成慢波离线状态的电路动力学。2)使用这些信息来评估在慢波和其他脱机状态下对电路动力学的操纵可能如何直接影响记忆巩固。3)对比和比较我们的记忆持久性活动依赖模型和更经典的分子突触模型。了解记忆的大脑机制可能是当今神经科学中最耐人寻味、也可能是最重要的问题之一。我们的研究将有助于塑造我们如何以最佳方式传递信息，以改善记忆力。我们研究项目的另一个重要而直接的贡献将是评估非常简单的操作，这些操作可能会对调节记忆强度和寿命产生深远影响。

My laboratory investigates the neural processes that underlie memory permanence (consolidation). We are most interested in the episodic subtype of memory which can be described as recollections of the "who, what, where, and when" aspects of unique experiences. These memories are dependent on the medial temporal lobe memory system which includes the broad inter-connections between the neocortex and the hippocampus in the brain. The patterns of neural activity in this extended circuit are not only important for encoding memories as they occur (that is, ONLINE memory encoding) but also for strengthening existing memories after the fact (that is, OFFLINE memory consolidation). Our laboratory is especially interested in how different patterns of offline spontaneous activity in the period just after active learning (especially during slow-wave activity like that occurring during sleep) may play a role in memory consolidation. The period just after learning has been demonstrated to be essential to the maintenance of memory itself. For example, following a particular novel episodic experience, hippocampal neuronal activity is known to "replay" the actual sequenced patterns that replicate those occurring during the actual experience itself. This replay may be a form of "neural rehearsal" since the more it occurs, the better future memory performance for that specific information actually is (and vice versa - interfering with replay worsens subsequent memory performance). This can be summarized by the saying: "practice makes permanent". The ability of the brain to engage in this rehearsal also appears to be state dependent, occurring only when the brain is actually "offline", for example during sleep. Thus, studying how this activity can take place is important to understand its role in consolidation. Our continuing program will focus on 3 main objectives: 1) To identify and characterise the circuit dynamics in the medial temporal lobe that shape slow-wave offline states using high-density multi-site neurophysiological methods and both chemo- and opto-genetic techniques. 2) To use this information to assess how manipulations of circuit dynamics during slow-wave and other offline states might directly affect memory consolidation. 3) To contrast and compare our activity-dependent model of memory permanence to the more classic molecular synaptic model. Understanding the brain mechanisms of memory is likely one of the most intriguing and potentially important questions in neuroscience today. Our research will help shape how we might optimally deliver information in order to ameliorate memory. Another important and direct contribution of our research program will be to evaluate very simple manipulations that might have profound influences on modulating memory strength and longevity.