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Crucial role for CA2 inputs in the sequential organization of CA1 time cells supporting memory [Neuroscience]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2021-01-19 , DOI: 10.1073/pnas.2020698118
Christopher J MacDonald 1, 2 , Susumu Tonegawa 1, 2, 3
Affiliation  

There is considerable evidence for hippocampal time cells that briefly activate in succession to represent the temporal structure of memories. Previous studies have shown that time cells can be disrupted while leaving place cells intact, indicating that spatial and temporal information can be coded in parallel. However, the circuits in which spatial and temporal information are coded have not been clearly identified. Here we investigated temporal and spatial coding by dorsal hippocampal CA1 (dCA1) neurons in mice trained on a classic spatial working-memory task. On each trial, the mice approached the same choice point on a maze but were trained to alternate between traversing one of two distinct spatial routes (spatial coding phase). In between trials, there was a 10-s mnemonic delay during which the mouse continuously ran in a fixed location (temporal coding phase). Using cell-type–specific optogenetic methods, we found that inhibiting dorsal CA2 (dCA2) inputs into dCA1 degraded time cell coding during the mnemonic delay and impaired the mouse’s subsequent memory-guided choice. Conversely, inhibiting dCA2 inputs during the spatial coding phase had a negligible effect on place cell activity in dCA1 and no effect on behavior. Collectively, our work demonstrates that spatial and temporal coding in dCA1 is largely segregated with respect to the dCA2–dCA1 circuit and suggests that CA2 plays a critical role in representing the flow of time in memory within the hippocampal network.



中文翻译:

CA2 输入在支持记忆的 CA1 时间细胞的顺序组织中的关键作用 [神经科学]

有大量证据表明海马时间细胞连续短暂地激活以代表记忆的时间结构。先前的研究表明,时间细胞可以被打乱,而位置细胞却完好无损,这表明空间和时间信息可以并行编码。然而,空间和时间信息被编码的电路还没有被清楚地识别出来。在这里,我们研究了受过经典空间工作记忆任务训练的小鼠背侧海马 CA1 (dCA1) 神经元的时间和空间编码。在每次试验中,老鼠在迷宫中接近相同的选择点,但被训练在穿越两条不同的空间路线之一(空间编码阶段)之间交替。在试炼之间,有一个 10 秒的记忆延迟,在此期间鼠标连续在固定位置运行(时间编码阶段)。使用细胞类型特异性光遗传学方法,我们发现抑制背侧 CA2 (dCA2) 输入到 dCA1 会降低记忆延迟期间的时间细胞编码,并损害小鼠随后的记忆引导选择。相反,在空间编码阶段抑制 dCA2 输入对 dCA1 中的位置细胞活性的影响可以忽略不计,对行为没有影响。总的来说,我们的工作表明 dCA1 中的空间和时间编码在很大程度上与 dCA2-dCA1 回路分离,并表明 CA2 在表示海马网络内记忆中的时间流动方面起着关键作用。我们发现抑制背侧 CA2 (dCA2) 输入到 dCA1 会降低记忆延迟期间的时间细胞编码,并损害小鼠随后的记忆引导选择。相反,在空间编码阶段抑制 dCA2 输入对 dCA1 中的位置细胞活性的影响可以忽略不计,对行为没有影响。总的来说,我们的工作表明 dCA1 中的空间和时间编码在很大程度上与 dCA2-dCA1 回路分离,并表明 CA2 在表示海马网络内记忆中的时间流动方面起着关键作用。我们发现抑制背侧 CA2 (dCA2) 输入到 dCA1 会降低记忆延迟期间的时间细胞编码,并损害小鼠随后的记忆引导选择。相反,在空间编码阶段抑制 dCA2 输入对 dCA1 中的位置细胞活性的影响可以忽略不计,对行为没有影响。总的来说,我们的工作表明 dCA1 中的空间和时间编码在很大程度上与 dCA2-dCA1 回路分离,并表明 CA2 在表示海马网络内记忆中的时间流动方面起着关键作用。

更新日期:2021-01-12
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