Center for Memory and Brain, Department of Psychology, Boston University, 2 Cummington Mall, Boston, Massachusetts.
Hippocampus. 2014 Jun;24(6):643-55. doi: 10.1002/hipo.22253. Epub 2014 Feb 19.
Grid cells of the medial entorhinal cortex exhibit a periodic and stable pattern of spatial tuning that may reflect the output of a path integration system. This grid pattern has been hypothesized to serve as a spatial coordinate system for navigation and memory function. The mechanisms underlying the generation of this characteristic tuning pattern remain poorly understood. Systemic administration of the muscarinic antagonist scopolamine flattens the typically positive correlation between running speed and entorhinal theta frequency in rats. The loss of this neural correlate of velocity, an important signal for the calculation of path integration, raises the question of what influence scopolamine has on the grid cell tuning as a read out of the path integration system. To test this, the spatial tuning properties of grid cells were compared before and after systemic administration of scopolamine as rats completed laps on a circle track for food rewards. The results show that the spatial tuning of the grid cells was reduced following scopolamine administration. The tuning of head direction cells, in contrast, was not reduced by scopolamine. This is the first report to demonstrate a link between cholinergic function and grid cell tuning. This work suggests that the loss of tuning in the grid cell network may underlie the navigational disorientation observed in Alzheimer's patients and elderly individuals with reduced cholinergic tone.
内侧缰状回皮层的网格细胞表现出周期性和稳定的空间调谐模式，这可能反映了一个路径整合系统的输出。这个网格模式被假设为导航和记忆功能的空间坐标系。然而，产生这种特征调谐模式的机制仍知之甚少。系统给予毒蕈碱拮抗剂东莨菪碱后，会使大鼠的跑动速度与缰状回θ频率之间的典型正相关变平。这种速度的神经相关物的缺失，是路径整合计算的一个重要信号，这就提出了一个问题，即东莨菪碱对网格细胞调谐作为路径整合系统的读出有什么影响。为了测试这一点，当大鼠在圆形轨道上为食物奖励而跑圈时，在给予东莨菪碱前后比较了网格细胞的空间调谐特性。结果表明，给予东莨菪碱后，网格细胞的空间调谐降低了。相比之下，头方向细胞的调谐并没有被东莨菪碱降低。这是第一个报告证明胆碱能功能与网格细胞调谐之间存在联系的报告。这项工作表明，网格细胞网络调谐的丧失可能是阿尔茨海默病患者和胆碱能张力降低的老年个体中观察到的导航迷失的基础。
