Neuronal basis, functional role and pathological relevance of grid cell-like representations in the human brain

人脑中网格细胞样表征的神经元基础、功能作用和病理相关性

• 批准号: 429281110
• 负责人: Professor Dr. Nikolai Axmacher
• 金额: --
• 依托单位: Abteilung Neuropsychologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/429281110?language=en
• 关键词: Neuronal; basis; functional; role; pathological

Grid cells were initially discovered in the entorhinal cortex (EC) of rodents and are characterized by hexagonally arranged (i.e., six-fold rotationally symmetric) spatial firing fields. They have been hypothesized to support spatial navigation by implementing a mechanism for path integration (PI).In humans, grid cells could be identified via single-unit recordings in presurgical epilepsy patients during virtual spatial navigation. In addition, several fMRI studies found indirect evidence for “grid cell-like representations” (GCLRs), a putative network-level signature of grid cells in the EC with six-fold rotational symmetry. More recently, we conducted intracranial EEG (iEEG) recordings in the EC of epilepsy patients during the same spatial navigation task and observed GCLRs based on the power of theta (4-8Hz) oscillations. Until now, however, a direct link between grid cells and GCLRs could not be established. Additional open questions concern the exact functional role of GCLRs for PI and their clinical relevance for understanding Alzheimer’s disease (AD), because neurodegeneration in AD has been proposed to start in EC. Here, we propose two studies to address these issues. In the first study, we will use iEEG and single-unit recordings via combined micro-/macro-electrodes to simultaneously measure action potentials and iEEG oscillations in presurgical epilepsy patients. Patients will perform a PI task in an open-field virtual environment. This study will allow us to directly link the activity of single grid cells to GCLRs. In the second study, we will conduct fMRI recordings in healthy young participants. Half of the participants carry the ɛ4 allele of the Apolipoprotein E gene (APOE4), the most important genetic risk for sporadic AD, while the other half consists of control participants. The fMRI study is composed of two experiments across two consecutive days. On the first day, participants will conduct a same spatial navigation task in the scanner that has been used before to identify GCLRs. Experiment two consists of the same path integration task as in the iEEG/single unit experiment. We will quantify the stability of fMRI GCLRs across the two experiments and relate them to performance in the two experiments and to the APOE genotype. Together, the two studies will provide a better understanding of the neuronal mechanisms of GCLRs, their functional role for PI, and their possible impairment in genetic AD risk carriers.

网格细胞最初在啮齿动物的内嗅皮层（EC）中发现，其特征在于六边形排列（即，六重旋转对称）空间激发场。它们被假设为通过实现路径整合（PI）的机制来支持空间导航。在人类中，网格细胞可以通过手术前癫痫患者在虚拟空间导航期间的单单位记录来识别。此外，一些功能磁共振成像研究发现了“网格细胞样表征”（GCLRs）的间接证据，这是EC中具有六重旋转对称的网格细胞的假定网络水平签名。最近，我们在癫痫患者的EC中进行了颅内EEG（iEEG）记录，并在相同的空间导航任务中观察了基于theta（4-8Hz）振荡功率的GCLR。然而，到目前为止，网格单元和GCLR之间的直接联系还无法建立。其他未决问题涉及GCLR对PI的确切功能作用及其与了解阿尔茨海默病（AD）的临床相关性，因为AD中的神经变性已被提出始于EC。在这里，我们提出两项研究来解决这些问题。在第一项研究中，我们将使用iEEG和通过组合微/宏电极的单单位记录，同时测量手术前癫痫患者的动作电位和iEEG振荡。患者将在开放式虚拟环境中执行PI任务。这项研究将使我们能够直接将单个网格细胞的活动与GCLR联系起来。在第二项研究中，我们将在健康的年轻参与者中进行fMRI记录。一半的参与者携带载脂蛋白E基因（APOE 4）的等位基因，这是散发性AD最重要的遗传风险，而另一半则由对照参与者组成。fMRI研究由连续两天的两个实验组成。在第一天，参与者将在扫描仪中进行相同的空间导航任务，之前曾用于识别GCLR。实验二由与iEEG/单个单元实验相同的路径整合任务组成。我们将量化两个实验中fMRI GCLR的稳定性，并将其与两个实验中的表现和APOE基因型相关。总之，这两项研究将提供一个更好的理解GCLRs的神经元机制，其功能作用PI，以及其可能的损害遗传AD风险携带者。