Cellular and network dynamics of temporal lobe memory structures

颞叶记忆结构的细胞和网络动力学

• 批准号: RGPIN-2021-02926
• 负责人: Dickson, Clayton
• 金额: $ 2.91万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=763996
• 关键词: Cellular; network; dynamics; temporal; lobe

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.

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，它可以被描述为对独特经历的“谁，什么，在哪里，什么时候”方面的回忆。这些记忆依赖于内侧颞叶记忆系统，该系统包括大脑新皮层和海马体之间广泛的相互联系。这个扩展回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，而且对事后的强化（即离线记忆巩固）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，不同的离线自发活动模式（特别是在睡眠期间发生的慢波活动期间）如何在记忆巩固中发挥作用。学习之后的这段时间对记忆本身的维持至关重要。例如，在经历了一段特殊的情节经历后，海马体神经元的活动会“重播”实际的序列模式，这些模式复制了在实际经历中发生的那些模式。这种重放可能是一种“神经排练”，因为它发生得越多，对特定信息的未来记忆表现就越好（反之亦然——干扰重放会使随后的记忆表现恶化）。这可以概括为一句话：“熟能生巧”。大脑参与这种排练的能力似乎也是依赖于状态的，只有在大脑处于“离线”状态时才会发生，比如在睡觉的时候。因此，研究这种活动是如何发生的对于理解它在巩固中的作用是很重要的。我们的后续计划将集中在3个主要目标上：1)使用高密度多位点神经生理学方法以及化学和光遗传技术识别和表征内侧颞叶中形成慢波离线状态的电路动力学。2)利用这些信息来评估在慢波和其他离线状态下的电路动力学操作如何直接影响记忆巩固。3)对比和比较我们的活动依赖的记忆持久性模型和更经典的分子突触模型。理解记忆的大脑机制可能是当今神经科学中最有趣和最重要的问题之一。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。我们研究项目的另一个重要而直接的贡献将是评估可能对调节记忆强度和寿命产生深远影响的非常简单的操作。