Department of Bioengineering, Howard Hughes Medical Institute, CNC Program, Stanford University, Stanford, CA 94305, USA.
Cell. 2011 Oct 28;147(3):678-89. doi: 10.1016/j.cell.2011.09.033. Epub 2011 Oct 20.
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.
主流理论认为，长期记忆是通过两个阶段的过程进行编码的，需要早期海马体的参与，然后是新皮层。啮齿动物的情境性恐惧记忆依赖于训练后立即的海马体，但不受海马体损伤或几周后药物抑制的影响。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，发现即使在训练几周后，通过 CA1 的时间精确光遗传学抑制也可以可逆地消除情境性恐惧记忆的回忆。当这种抑制延长到与典型的药物抑制时间过程相匹配时，远程海马体的依赖性转变为海马体独立性，这表明长期记忆检索通常依赖于海马体，但可以自适应地转移到替代结构。进一步揭示了记忆检索所需机制的可塑性，我们证实了前扣带皮层（ACC）在远程时间尺度上的重要性，并暗示 CA1 参与了远程回忆时的 ACC 募集。
