Department of Neurology, Center for Neuroscience, University of California Davis, Davis, CA 95616, USA.
Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, UC Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA.
Neuron. 2018 Mar 7;97(5):1187-1198.e4. doi: 10.1016/j.neuron.2018.01.039.
The entorhinal cortex (EC) is among the earliest brain areas to deteriorate in Alzheimer's disease (AD). However, the extent to which functional properties of the EC are altered in the aging brain, even in the absence of clinical symptoms, is not understood. Recent human fMRI studies have identified a functional dissociation within the EC, similar to what is found in rodents. Here, we used high-resolution fMRI to identify a specific hypoactivity in the anterolateral EC (alEC) commensurate with major behavioral deficits on an object pattern separation task in asymptomatic older adults. Only subtle deficits were found in a comparable spatial condition, with no associated differences in posteromedial EC between young and older adults. We additionally linked this condition to dentate/CA3 hyperactivity, and the ratio of activity between the regions was associated with object mnemonic discrimination impairment. These results provide novel evidence of alEC-dentate/CA3 circuit dysfunction in cognitively normal aged humans.
内嗅皮层（entorhinal cortex，EC）是阿尔茨海默病（Alzheimer's disease，AD）最早受损的大脑区域之一。然而，在没有临床症状的情况下，衰老大脑中 EC 的功能特性会发生多大程度的改变尚不清楚。最近的人类 fMRI 研究在 EC 内发现了一种功能上的分离，类似于在啮齿动物中发现的情况。在这里，我们使用高分辨率 fMRI 来识别无症状老年成年人在进行物体模式分离任务时，其前外侧内嗅皮层（anterolateral entorhinal cortex，alEC）特定的活动不足，这与主要行为缺陷相吻合。在类似的空间条件下仅发现了细微的缺陷，年轻和老年成年人之间在后内侧内嗅皮层（posteromedial entorhinal cortex）没有差异。我们还将这种情况与齿状回/CA3 过度活跃联系起来，并且区域之间的活动比率与物体记忆辨别障碍有关。这些结果为认知正常的老年人群中 alEC-齿状回/CA3 电路功能障碍提供了新的证据。
