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

海马结构(HF)是最高水平的联合皮质。如果没有功能正常的HF，新大脑皮层(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性知识时会受到严重损害。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，HF是最被了解的大脑系统之一，但对于HF外流对NC的影响知之甚少。这一研究方案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动力学以及信息存储和检索。为了实现这一点，我们将利用现代神经科学工具包中的一些最先进的遗传学、分子、光学和电子技术，结合HF-NC背投几乎完全是单方面的关键解剖学事实。这种片面性，再加上年轻成年啮齿动物的单侧HF损害不会导致严重的行为损害的事实，使得强大的受试者内实验设计能够在相同的动物受试者中比较NC的神经动力学和编码过程，以及(主要)没有HF的直接影响。例如，单侧HF损害阻止了由于单方面丰富的环境而导致的NC结构变化。这项研究的目标包括确定干扰高频向NC的背投影是否影响1)通过经验依赖的、2时间点的、即刻早期基因(IEG)激活观察到的NC II和III层细胞的空间上下文依赖性；2)利用双侧神经系综记录的NC重新激活最近的活动模式；3)在活体2-P显微镜下观察到的II和III层树突棘的经验依赖性变化；4)局部场活动的伽马频段半球间一致性；5)使用电压敏感染料和细胞特异性钙+成像来观察全球NC的动力学和感觉反应。我们将使用逆行标记加IEG分析来研究标记的HF背投射细胞的编码特性，以及使用跨突触病毒载体标记加IEG分析和体内钙成像来研究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.