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

海马结构（hippocampal formation，HF）是最高层的联合皮层。如果没有功能性HF，新皮层（NC）在形成或检索特定事件的记忆或从这些记忆中提取一般知识方面严重受损。 尽管HF在其细胞和分子生物学、突触可塑性、神经动力学和编码过程方面是最好理解的脑系统之一，但是关于HF流出对NC的影响知之甚少。 这项研究计划的中心主题和长期目标是阐明高频反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包中一些最先进的遗传、分子、光学和电子技术，结合HF-NC反向投射几乎完全是单侧的关键解剖学事实。 这种单侧性，再加上年轻成年啮齿动物单侧HF病变不会导致严重的行为障碍的事实，使强大的，受试者内的实验设计，允许比较的神经动力学和编码过程在NC与（很大程度上）没有直接HF的影响，在相同的动物科目。例如，单侧HF病变阻止了由于单侧富集环境引起的NC结构变化。本研究的目的包括确定干扰HF反向投射到NC是否影响1）通过经验依赖性、2-时间点、立即早期基因（IEG）激活观察到的NC层II和III细胞的空间背景依赖性; 2）使用双侧神经系综记录的近期活动模式的NC再激活; 3）在体内用2-P显微镜观察到的第II层和第III层树突棘中的经验依赖性变化; 4）局部场活动的γ带半球间一致性; 5）使用电压敏感染料和细胞特异性Ca++成像的整体NC动力学和感觉反应性。我们将研究标记的HF背投影细胞的编码特性，使用逆行标记加IEG分析，和HF受体细胞，使用跨突触病毒载体标记加IEG分析和体内Ca++成像。

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.