Neurobiology Section and Center for Neural Circuits and Behavior, University of California, San Diego, La Jolla, CA 92093, USA; Division of Neurobiology, Department Biology II, Ludwig-Maximilians-Universität, Munich, Germany.
Neurobiol Learn Mem. 2013 Nov;106:324-33. doi: 10.1016/j.nlm.2013.05.007. Epub 2013 Jun 4.
Temporally graded retrograde amnesia is observed in human patients with medial temporal lobe lesions as well as in animal models of medial temporal lobe lesions. A time-limited role for these structures in memory recall has also been suggested by the observation that the rodent hippocampus and entorhinal cortex are activated during the retrieval of recent but not of remote memories. One notable exception is the recall of remote memories for platform locations in the water maze, which requires an intact hippocampus and results in hippocampal activation irrespective of the age of the memory. These findings raise the question whether the hippocampus is always involved in the recall of spatial memories or, alternatively, whether it might be required for procedural computations in the water maze task, such as for calculating a path to a hidden platform. We performed spatial memory testing in radial maze tasks to distinguish between these possibilities. Radial maze tasks require a choice between spatial locations on a center platform and thus have a lesser requirement for navigation than the water maze. However, we used a behavioral design in the radial maze that retained other aspects of the standard water maze task, such as the use of multiple start locations and retention testing in a single trial. Using the immediate early gene c-fos as a marker for neuronal activation, we found that all hippocampal subregions were more activated during the recall of remote compared to recent spatial memories. In areas CA3 and CA1, activation during remote memory testing was higher than in rats that were merely reexposed to the testing environment after the same time interval. Conversely, Fos levels in the dentate gyrus were increased after retention testing to the extent that was also observed in the corresponding exposure control group. This pattern of hippocampal activation was also obtained in a second version of the task that only used a single start arm instead of multiple start arms. The CA3 and CA1 activation during remote memory recall is consistent with the interpretation that an older memory might require increased pattern completion and/or relearning after longer time intervals. Irrespective of whether the hippocampus is required for remote memory recall, the hippocampus might engage in computations that either support recall of remote memories or that update remote memories.
内侧颞叶损伤的人类患者和内侧颞叶损伤的动物模型均表现出时间梯度逆行性遗忘。观察到啮齿动物海马体和内嗅皮层在回忆近期记忆而非远期记忆时被激活，这也提示这些结构在记忆回忆中具有时间限制的作用。一个值得注意的例外是在水迷宫中对平台位置的远期记忆的回忆，这需要完整的海马体，并导致海马体的激活，而与记忆的年龄无关。这些发现提出了一个问题，即海马体是否总是参与空间记忆的回忆，或者它是否可能需要在水迷宫任务中的程序性计算，例如计算到隐藏平台的路径。我们在放射状迷宫任务中进行了空间记忆测试，以区分这些可能性。放射状迷宫任务需要在中央平台上的空间位置之间进行选择，因此比水迷宫任务的导航要求低。然而，我们在放射状迷宫中使用了一种保留了标准水迷宫任务其他方面的行为设计，例如使用多个起始位置和在单个试验中进行保留测试。使用即刻早期基因 c-fos 作为神经元激活的标志物，我们发现所有海马亚区在回忆远期空间记忆时比回忆近期空间记忆时的激活程度更高。在 CA3 和 CA1 区，在进行远期记忆测试时的激活程度高于在经过相同时间间隔后仅重新暴露于测试环境的大鼠。相反，在进行保留测试后，齿状回中的 Fos 水平增加到与相应的暴露对照组中观察到的程度。在仅使用单个起始臂而不是多个起始臂的任务的第二个版本中也获得了这种海马激活模式。在进行远程记忆回忆时 CA3 和 CA1 的激活与以下解释一致，即较旧的记忆可能需要在更长的时间间隔后增加模式完成和/或重新学习。无论海马体是否需要进行远程记忆回忆，海马体可能参与支持远程记忆回忆或更新远程记忆的计算。
