PDF(Pubmed)
Abstract：
The ability to remember changes in the surroundings is fundamental for daily life. It has been proposed that novel events producing dopamine release in the hippocampal CA1 region could modulate spatial memory formation. However, the role of hippocampal dopamine increase on weak or strong spatial memories remains unclear. We show that male mice exploring two objects located in a familiar environment for 5 min created a short-term memory (weak) that cannot be retrieved 1 d later, whereas 10 min exploration created a long-term memory (strong) that can be retrieved 1 d later. Remarkably, hippocampal dopamine elevation during the encoding of weak object location memories (OLMs) allowed their retrieval 1 d later but dopamine elevation during the encoding of strong OLMs promoted the preference for a familiar object location over a novel object location after 24 h. Moreover, dopamine uncaging after the encoding of OLMs did not have effect on weak memories whereas on strong memories diminished the exploration of the novel object location. Additionally, hippocampal dopamine elevation during the retrieval of OLMs did not allow the recovery of weak memories and did not affect the retrieval of strong memory traces. Finally, dopamine elevation increased hippocampal theta oscillations, indicating that dopamine promotes the recurrent activation of specific groups of neurons. Our experiments demonstrate that hippocampal dopaminergic modulation during the encoding of OLMs depends on memory strength indicating that hyperdopaminergic levels that enhance weak experiences could compromise the normal storage of strong memories.
摘要：
记住周围环境变化的能力是日常生活的基础。有人提出，在海马CA1区产生多巴胺释放的新事件可以调节空间记忆的形成。然而,海马多巴胺增加对弱或强空间记忆的作用尚不清楚。我们表明，雄性小鼠在熟悉的环境中探索两个物体5分钟会产生短期记忆（弱），一天后无法恢复，而10分钟的探索创造了一个长期记忆（强），可以在一天后恢复。值得注意的是,在弱对象位置记忆（OLM）的编码过程中海马多巴胺的升高允许一天后进行检索，但是在强OLM的编码过程中多巴胺的升高促使人们在24小时后更喜欢熟悉的对象位置而不是新的对象位置。此外，OLM编码后的多巴胺解串对弱记忆没有影响，而对强记忆则减少了对新物体位置的探索。此外,OLM检索过程中海马多巴胺升高不允许弱记忆的恢复，也不影响强记忆痕迹的检索。最后,多巴胺升高增加了海马theta振荡，表明多巴胺促进特定神经元组的反复激活。我们的实验表明，OLM编码过程中的海马多巴胺能调节取决于记忆强度，表明增强弱体验的高多巴胺能水平可能会损害强记忆的正常存储。重要性声明多巴胺水平的增加与认知增强有关。由新颖性暴露引起的海马多巴胺升高已被提出作为一种增强记忆的策略，其基础是观察到令人惊讶的事件会产生长时间记住的闪光灯记忆。然而,高多巴胺能水平也可能是适应不良记忆的基础，例如对创伤经历的非期望保存。我们的实验表明，在空间记忆的编码过程中，背侧海马中的多巴胺升高具有矛盾的作用，虽然弱记忆的增强允许它们被检索，强记忆的多巴胺能调节限制了通过环境变化来修改先前存在的空间记忆的能力。我们得出的结论是，通过多巴胺增强来增强认知功能必须考虑记忆形成的各个方面。
