Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Cell Rep. 2018 Oct 9;25(2):288-295.e3. doi: 10.1016/j.celrep.2018.09.033.
Social isolation (SI) has detrimental effects on human and animal cognitive functions. In particular, acute isolation in adult mice impairs social recognition memory (SRM). Previous accounts of this impairment have focused primarily on memory consolidation. However, the current study suggests that impaired SRM results from enhanced forgetting. SI accelerates SRM decay without affecting memory formation. The impairment is caused by elevated Rac1 activity in the hippocampus. Using adeno-associated-virus-based genetic manipulation, we found that inhibition of Rac1 activity blocked forgetting of SRM in isolated adult mice, whereas activation of Rac1 accelerated forgetting in group-housed mice. Moreover, resocialization reversed the accelerated forgetting following isolation in correlation with suppression of Rac1 activity. In addition, accelerated long-term potentiation (LTP) decay in isolated mice brain slices was rescued by inhibition of Rac1 activity. Taken together, the findings lead us to conclude that social memory deficits in isolated mice are mediated by enhanced Rac1-dependent forgetting.
社交隔离（SI）对人类和动物的认知功能有不利影响。特别是，成年小鼠的急性隔离会损害社交识别记忆（SRM）。之前对这种损伤的描述主要集中在记忆巩固上。然而，本研究表明，受损的 SRM 是由于增强的遗忘所致。SI 加速了 SRM 的衰减，而不影响记忆的形成。这种损伤是由海马 Rac1 活性升高引起的。通过腺相关病毒的遗传操作，我们发现抑制 Rac1 活性可以阻断孤立成年小鼠的 SRM 遗忘，而 Rac1 的激活则加速了群居小鼠的遗忘。此外，重新社交化与 Rac1 活性的抑制相关，可逆转隔离后的加速遗忘。此外，抑制 Rac1 活性可挽救孤立小鼠脑片的长时程增强（LTP）衰减加速。总之，这些发现使我们得出结论，孤立小鼠的社交记忆缺陷是由增强的 Rac1 依赖性遗忘介导的。
