Wang Melissa E, Yuan Robin K, Keinath Alexander T, Ramos Álvarez Manuel M, Muzzio Isabel A
Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and.
Department of Psychology, Universidad de Jaén, 23071 Jaén, Spain.
J Neurosci. 2015 Jun 17;35(24):9122-36. doi: 10.1523/JNEUROSCI.4477-14.2015.
The extinction of learned fear is a hippocampus-dependent process thought to embody new learning rather than erasure of the original fear memory, although it is unknown how these competing contextual memories are represented in the hippocampus. We previously demonstrated that contextual fear conditioning results in hippocampal place cell remapping and long-term stabilization of novel representations. Here we report that extinction learning also induces place cell remapping in C57BL/6 mice. Specifically, we observed cells that preferentially remapped during different stages of learning. While some cells remapped in both fear conditioning and extinction, others responded predominantly during extinction, which may serve to modify previous representations as well as encode new safe associations. Additionally, we found cells that remapped primarily during fear conditioning, which could facilitate reacquisition of the original fear association. Moreover, we also observed cells that were stable throughout learning, which may serve to encode the static aspects of the environment. The short-term remapping observed during extinction was not found in animals that did not undergo fear conditioning, or when extinction was conducted outside of the conditioning context. Finally, conditioning and extinction produced an increase in spike phase locking to the theta and gamma frequencies. However, the degree of remapping seen during conditioning and extinction only correlated with gamma synchronization. Our results suggest that the extinction learning is a complex process that involves both modification of pre-existing memories and formation of new ones, and these traces coexist within the same hippocampal representation.
习得性恐惧的消退是一个依赖海马体的过程，被认为体现了新的学习，而非消除原始恐惧记忆，尽管目前尚不清楚这些相互竞争的情境记忆在海马体中是如何表征的。我们之前证明，情境恐惧条件作用会导致海马体位置细胞重新映射以及新表征的长期稳定。在此我们报告，消退学习也会在C57BL/6小鼠中诱导位置细胞重新映射。具体而言，我们观察到在学习的不同阶段优先重新映射的细胞。虽然一些细胞在恐惧条件作用和消退过程中都发生了重新映射，但其他细胞主要在消退期间做出反应，这可能有助于修改先前的表征以及编码新的安全关联。此外，我们发现主要在恐惧条件作用期间重新映射的细胞，这可能有助于重新获得原始恐惧关联。而且，我们还观察到在整个学习过程中保持稳定的细胞，这可能有助于编码环境的静态方面。在未经历恐惧条件作用的动物中，或者在条件作用情境之外进行消退时，未发现消退期间观察到的短期重新映射。最后，条件作用和消退导致了尖峰相位与θ波和γ波频率的锁定增加。然而，条件作用和消退期间观察到的重新映射程度仅与γ波同步相关。我们的结果表明，消退学习是一个复杂的过程，涉及对先前存在记忆的修改和新记忆的形成，并且这些痕迹共存于同一海马体表征中。
