Hippocampal cortical interactions and the extraction of knowledge from episodic memory

我的研究项目主要集中在记忆的神经计算基础和神经元群体之间的动态相互作用，这些相互作用导致了大脑创造其自适应模型的能力。在过去的35年里，我在理解中枢突触可塑性机制、空间信息处理、皮质-海马体相互作用和记忆巩固方面做出了重大贡献，并在系统神经科学研究方面取得了重大进展。在这项工作中，我培养了33名优秀的研究生和37名博士后，其中大部分人在各大大学从事研究工作。在接下来的5年里，我的总体计划（包括其他支持）将为至少4名本科生，10名研究生和7名博士后提供培训，因为我们将继续研究海马背投射到新皮层对神经编码和神经可塑性的影响。理解这种影响是理解为什么在海马体功能缺失的情况下，新皮层无法形成新的记忆或有效地从经验中提取一般知识的关键。这也是理解一种可能对信息和计算机技术产生深远影响的计算知识获取和表示模式的关键。*******“海马体（HC）对新皮层（NC）有什么作用？”这个问题在三个特定的子主题下得到解决：1)HC如何影响NC神经元的实际编码特性？特别是，某些NC区域的对象编码和行为的明显空间调制是否继承自HC中的“位置编码”？NC编码统计是否会随着大脑对世界模型的改进而改变？ HC是否会促成这种改变？2)在休息和慢波睡眠中观察到的NC记忆痕迹的再激活在多大程度上依赖于HC输出？新记忆的依赖性与恢复或自发检索的旧记忆相比是否不同？对于新记忆来说，是HC本身需要NC再激活，还是仅仅需要在大范围内同步皮质再激活？在记忆再激活过程中，脑脊液流出最强烈地激活NC的哪一部分？当记忆逐渐巩固时，中脑和中脑记忆再激活之间的相对时间是否会发生变化（即，中脑是否首先引导中脑，然后跟随中脑）？3) HC对于NC学习相关的树突脊柱可塑性是必要的吗？HC是否对NC神经可塑性至关重要的NC神经营养因子的表达有调节作用？*******这些问题是通过多神经元记录的各种组合来解决的，使用电生理和光学成像方法，新皮层电压记录，体内NC树突棘的结构和功能成像，以及神经营养因子的免疫化学定量，在HC功能完整或失活的动物中。******

My research program focusses on the neuro-computational basis of memory and the dynamic interactions among neuronal populations that lead to the brain's ability to create an adaptive model of its. Over the past 35 years, I have made major contributions to understanding central synaptic plasticity mechanisms, spatial information processing, cortico-hippocampal interactions and memory consolidation, and significantly advanced technologies for systems neuroscience investigation. In the course of this work I have provided outstanding training to 33 graduate students, and 37 postdocs, most of whom are pursuing research careers at major universities. Over the next 5 years, my overall programme (including other support) will provide training for at least 4 undergrads, 10 graduates and 7 postdocs, as we continue to study the impact of hippocampal back projections to the neocortex on neural coding and neural plasticity in that structure. Understanding this impact is key to understanding why, in the absence of a functional hippocampus, the neocortex is unable to form new memories or to extract general knowledge from experience efficiently. It is also key to understanding a mode of computational knowledge acquisition and representation that may have far reaching impacts on information and computer technology.******* "What does the hippocampus (HC) do for neocortex (NC)?" This question is addressed under three specific subtopics: 1) How does HC affect the actual coding properties of NC neurons? In particular, is the apparent spatial modulation of object encoding and behavior in some NC regions inherited from "place coding" in HC? Do NC coding statistics change as the brain refines its model of the world, and does HC enable such changes? 2) To what degree does the reactivation of memory traces observed in NC during rest and slow-wave-sleep depend on HC output? Is the dependence different for new memories compared to reinstated or spontaneously retrieved old memories? For new memories, is HC required for NC reactivation per se, or rather is it merely required for synchronizing cortical reactivation over broad areas? Which parts of NC are most strongly activated by HC outflow during memory reactivation? Does the relative timing between NC and HC memory reactivation change as memories gradually become consolidated (i.e., does HC initially lead HC and subsequently follow it)? 3) Is HC necessary for learning-associated dendritic spine plasticity in NC? Does HC contribute to the regulation of expression of NC neurotrophins which are crucial to neuroplasticity in NC?******* These questions are addressed using various combinations of multi-neuron recording, using electrophysiological and optical imaging methods, neocortical voltage recording, structural and functional imaging of NC dendritic spines in vivo, and immunochemical quantification of neurotrophic factors, in animals with intact or inactivated HC function.******