"The hippocampal indexing theory: impact of hippocampal-neocortical backprojections on neocortical neurodynamics, plasticity and coding"

海马体形成（HF）是最高级别的联合皮层。如果HF功能不正常，新皮层（NC）在形成或提取特定事件的记忆或从这些记忆中提取一般知识方面受到严重损害。尽管在细胞和分子生物学、突触可塑性、神经动力学和编码过程方面，心衰是人们最了解的脑系统之一，但人们对心衰流出对心衰的影响知之甚少。本研究计划的中心主题和长期目标是阐明高频反向投影实际上如何影响NC动力学和信息存储和检索。为了实现这一目标，我们将利用现代神经科学工具箱中一些最先进的遗传、分子、光学和电子技术，并结合HF-NC背投影几乎完全是单侧的关键解剖学事实。这种单侧性，加上年轻成年啮齿动物单侧HF病变不会导致严重行为障碍的事实，使强大的受试者内实验设计成为可能，可以在同一动物受试者中比较有和（很大程度上）没有直接HF影响的NC的神经动力学和编码过程。例如，单侧HF病变阻止了单侧富集环境导致的NC结构改变。本研究计划的目的包括确定干扰高频反向投射到NC是否会影响1)通过经验依赖、2时间点、即时早期基因（IEG）激活观察到的NC层II和III细胞的空间环境依赖性；2)利用双侧神经集合记录对近期活动模式进行NC再激活；3)用2-P显微镜观察体内第II层和第III层树突棘的经验依赖性变化；局部磁场活动的伽马波段半球间相干性；5)使用电压敏感染料和细胞特异性Ca++成像的全局NC动态和感觉反应。我们将使用逆行标记加IEG分析的方法研究标记的HF反向投射细胞的编码特性，并使用跨突触病毒载体标记加IEG分析和体内ca++成像的方法研究HF受体细胞的编码特性。

The hippocampal formation (HF) is the highest level of association cortex. Without a functioning HF, the neocortex (NC) is severely impaired in forming or retrieving memories for specific events or extracting generalized knowledge from these memories. Although the HF is among the best understood brain systems in terms of its cell and molecular biology, synaptic plasticity, neural dynamics and coding processes, very little is known about the impact of HF outflow on the NC. The central theme and long-term goal of this research programme is to elucidate how HF back-projections actually affect NC dynamics and information storage and retrieval. To accomplish this, we will take advantage of some of the most advanced genetic, molecular, optical and electronic technologies in the toolkit of modern neuroscience, in combination with the key anatomical fact that HF-NC back-projections are almost exclusively unilateral. This unilaterality, plus the fact that unilateral HF lesions in young adult rodents do not result in severe behavioural impairments, enables powerful, within-subject experimental designs which allow comparison of neural dynamics and coding processes in NC with and (largely) without direct HF influences, in the same animal subjects. For example, unilateral HF lesions prevent NC structural changes due to enriched environments unilaterally. The objectives of this research programme include determining whether interfering with HF back-projections to NC affect 1) spatial context dependence of NC Layer II & III cells observed with experience-dependent, 2-time point, immediate-early gene (IEG) activation; 2) NC reactivation of recent activity patterns using bilateral neural ensemble recording; 3) experience-dependent changes in Layer II & III dendritic spines observed with 2-P microscopy in vivo; 4) gamma band interhemispheric coherence of local field activity; 5) global NC dynamics and sensory responsiveness using voltage-sensitive dye and cell specific Ca++ imaging. We will study the coding properties of tagged HF back-projection cells, using retrograde labelling plus IEG analysis, and of HF recipient cells, using trans-synaptic viral vector labelling plus IEG analysis and in vivo Ca++ imaging.