Dynamics of Retrieval Strategies for Remote Memories
Dynamics of Retrieval Strategies for Remote Memories
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DOI：
10.1016/j.cell.2011.09.033
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发表时间：
2011-10-28
期刊：
影响因子：
64.5
通讯作者：
Deisseroth, Karl
中科院分区：
文献类型：
--
作者：
Goshen, Inbal;Brodsky, Matthew;Deisseroth, Karl
流行的理论认为，长期记忆是通过一个两阶段的过程来编码的，这个过程需要海马体的早期参与，然后是新皮层。啮齿类动物的情境恐惧记忆在训练后立即依赖海马体，但在几周后不受海马体损伤或药物抑制的影响。通过快速光遗传学方法，我们研究了海马CA1兴奋性神经元对远程记忆的实时贡献，并发现即使在训练后几周，情境恐惧记忆的回忆也可以通过暂时精确的CA1光遗传学抑制而可逆地消除。当这种抑制延长到与药物抑制的典型时间过程相匹配时，远端海马依赖转变为海马独立，这表明长期记忆的恢复通常依赖于海马，但可以自适应地转移到其他结构。我们进一步揭示了记忆回忆所需机制的可塑性，证实了前扣带皮层（ACC）在远程时间尺度上的重要性，并暗示CA1参与ACC在远程回忆中的募集。
Prevailing theory suggests that long-term memories are encoded via a two-phase process requiring early involvement of the hippocampus followed by the neocortex. Contextual fear memories in rodents rely on the hippocampus immediately following training but are unaffected by hippocampal lesions or pharmacological inhibition weeks later. With fast optogenetic methods, we examine the real-time contribution of hippocampal CA1 excitatory neurons to remote memory and find that contextual fear memory recall, even weeks after training, can be reversibly abolished by temporally precise optogenetic inhibition of CA1. When this inhibition is extended to match the typical time course of pharmacological inhibition, remote hippocampus dependence converts to hippocampus independence, suggesting that long-term memory retrieval normally depends on the hippocampus but can adaptively shift to alternate structures. Further revealing the plasticity of mechanisms required for memory recall, we confirm the remote-timescale importance of the anterior cingulate cortex (ACC) and implicate CA1 in ACC recruitment for remote recall.