School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Elife. 2024 Nov 5;12:RP92860. doi: 10.7554/eLife.92860.
Memories are stored as ensembles of engram neurons and their successful recall involves the reactivation of these cellular networks. However, significant gaps remain in connecting these cell ensembles with the process of forgetting. Here, we utilized a mouse model of object memory and investigated the conditions in which a memory could be preserved, retrieved, or forgotten. Direct modulation of engram activity via optogenetic stimulation or inhibition either facilitated or prevented the recall of an object memory. In addition, through behavioral and pharmacological interventions, we successfully prevented or accelerated forgetting of an object memory. Finally, we showed that these results can be explained by a computational model in which engrams that are subjectively less relevant for adaptive behavior are more likely to be forgotten. Together, these findings suggest that forgetting may be an adaptive form of engram plasticity which allows engrams to switch from an accessible state to an inaccessible state.
记忆被存储为记忆神经元的集合，它们的成功回忆涉及到这些细胞网络的重新激活。然而，将这些细胞集合与遗忘过程联系起来仍然存在很大的差距。在这里，我们利用了一种物体记忆的小鼠模型，并研究了在什么条件下可以保存、检索或遗忘记忆。通过光遗传学刺激或抑制直接调节记忆痕迹的活性，促进或阻止了对物体记忆的回忆。此外，通过行为和药理学干预，我们成功地阻止或加速了对物体记忆的遗忘。最后，我们表明，这些结果可以用一个计算模型来解释，在这个模型中，对于适应性行为主观上不太重要的记忆痕迹更容易被遗忘。总之，这些发现表明，遗忘可能是记忆痕迹可塑性的一种适应形式，它允许记忆痕迹从可访问状态切换到不可访问状态。
