School of Life Sciences, Tsinghua University, Beijing 100084, People's Republic of China.
McGovern Institute of Brain Research, Tsinghua University, Beijing 100084, People's Republic of China.
Proc Natl Acad Sci U S A. 2022 Apr 12;119(15):e2116844119. doi: 10.1073/pnas.2116844119. Epub 2022 Apr 4.
In pathological or artificial conditions, memory can be formed as silenced engrams that are unavailable for retrieval by presenting conditioned stimuli but can be artificially switched into the latent state so that natural recall is allowed. However, it remains unclear whether such different states of engrams bear any physiological significance and can be switched through physiological mechanisms. Here, we show that an acute social reward experience switches the silent memory engram into the latent state. Conversely, an acute social stress causes transient forgetting via turning a latent memory engram into a silent state. Such emotion-driven bidirectional switching between latent and silent states of engrams is mediated through regulation of Rac1 activity–dependent reversible forgetting in the hippocampus, as stress-activated Rac1 suppresses retrieval, while reward recovers silenced memory under amnesia by inhibiting Rac1. Thus, data presented reveal hippocampal Rac1 activity as the basis for emotion-mediated switching between latent and silent engrams to achieve emotion-driven behavioral flexibility.
在病理或人为条件下，记忆可以形成沉默的印痕，通过呈现条件刺激，这些印痕无法被检索，但可以被人为地转换为潜伏状态，从而允许自然回忆。然而，目前尚不清楚这些不同状态的印痕是否具有生理意义，并且可以通过生理机制进行转换。在这里，我们表明急性社会奖励体验将沉默的记忆印痕转换为潜伏状态。相反，急性社会压力通过将潜伏记忆印痕转换为沉默状态导致短暂遗忘。这种印痕的潜伏和沉默状态之间的情绪驱动的双向转换是通过调节海马 Rac1 活性依赖性的可逆遗忘来介导的，因为应激激活的 Rac1 抑制了检索，而奖励通过抑制 Rac1 在健忘症下恢复沉默的记忆。因此，所呈现的数据表明，海马 Rac1 活性是潜伏和沉默印痕之间情绪介导转换的基础，以实现情绪驱动的行为灵活性。
