Artificially Enhancing and Suppressing Hippocampus-Mediated Memories
Artificially Enhancing and Suppressing Hippocampus-Mediated Memories
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DOI：
10.1016/j.cub.2019.04.065
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发表时间：
2019-06-03
期刊：
影响因子：
9.2
通讯作者：
Ramirez, Steve
中科院分区：
文献类型：
--
作者：
Chen, Briana K.;Murawski, Nathen J.;Ramirez, Steve
新出现的证据表明，不同的海马区不同地驱动认知和情绪[1，2]；背侧区域编码空间、时间和背景信息[3-5]，而腹侧区域调节压力反应[6]、焦虑相关行为[7，8]和情绪状态[8-10]。虽然之前的研究表明，光学操作背侧海马区的细胞可以驱动积极和消极记忆的行为表达，但尚不清楚腹侧海马区细胞活动的变化是否能够驱动这种行为[11-14]。研究横跨纵轴的不同的海马体记忆调节行为的程度可以帮助理解与压力相关的精神疾病，这些疾病已知会影响情绪、记忆和认知[15]。在这里，我们询问沿着小鼠海马体背腹轴标记和刺激细胞是否可以尖锐地、长期地和不同地促进特定背景的行为。以前在记忆形成过程中活跃的背侧和腹侧海马区细胞的急性重新激活推动了冰冻行为、位置回避和位置偏好。此外，对背侧或腹侧海马区恐惧记忆的长期刺激分别产生背景特定的恐惧反应的减弱或增强，从而显示出记忆沿海马体纵轴的双向和背景特定的调制。恐惧记忆抑制与提取过程中活跃的海马细胞减少有关，而恐惧记忆增强与杏仁基底外侧核活动增加有关。总而言之，我们的数据表明，整个海马区的离散细胞集提供了足够的关键节点，足以双向重新编程记忆的神经和行为表达。
Emerging evidence indicates that distinct hippocampal domains differentially drive cognition and emotion [1, 2]; dorsal regions encode spatial, temporal, and contextual information [3-5 ], whereas ventral regions regulate stress responses [6], anxiety-related behaviors [7, 8], and emotional states [8-10 ]. Although previous studies demonstrate that optically manipulating cells in the dorsal hippocampus can drive the behavioral expression of positive and negative memories, it is unknown whether changes in cellular activity in the ventral hippocampus can drive such behaviors [11-14]. Investigating the extent to which distinct hippocampal memories across the longitudinal axis modulate behavior could aid in the understanding of stress-related psychiatric disorders known to affect emotion, memory, and cognition [15]. Here, we asked whether tagging and stimulating cells along the dorsoventral axis of the mouse hippocampus could acutely, chronically, and differentially promote context-specific behaviors. Acute reactivation of both dorsal and ventral hippocampus cells that were previously active during memory formation drove freezing behavior, place avoidance, and place preference. Moreover, chronic stimulation of dorsal or ventral hippocampal fear memories produced a context-specific reduction or enhancement of fear responses, respectively, thus demonstrating bi-directional and context-specific modulation of memories along the longitudinal axis of the hippocampus. Fear memory suppression was associated with a reduction in hippocampal cells active during retrieval, while fear memory enhancement was associated with an increase in basolateral amygdala activity. Together, our data demonstrate that discrete sets of cells throughout the hippocampus provide key nodes sufficient to bi-directionally reprogram both the neural and behavioral expression of memory.