Psychology Department, McGill University, 1205 Avenue Drive Penfield, Montreal, QC H3A 1B1, Canada.
Centre for Clinical Brain Sciences, University of Edinburgh, 49 Little France Crescent, Chancellor's Building GU507c, Edinburgh EH16 4SB, UK.
Curr Biol. 2018 Sep 24;28(18):2900-2909.e5. doi: 10.1016/j.cub.2018.07.037. Epub 2018 Sep 6.
The neurobiology of memory formation has been studied primarily in experimentally naive animals, but the majority of learning unfolds on a background of prior experience. Considerable evidence now indicates that the brain processes initial and subsequent learning differently. In rodents, a first instance of contextual fear conditioning requires NMDA receptor (NMDAR) activation in the dorsal hippocampus, but subsequent conditioning to another context does not. This shift may result from a change in molecular plasticity mechanisms or in the information required to learn the second task. To clarify how related events are encoded, it is critical to identify which aspect of a first task engages NMDAR-independent learning and the brain regions that maintain this state. Here, we show in rats that the requirement for NMDARs in hippocampus depends neither on prior exposure to context nor footshock alone but rather on the procedural similarity between two conditioning tasks. Importantly, NMDAR-independent learning requires the memory of the first task to remain hippocampus dependent. Furthermore, disrupting memory maintenance in the anterior cingulate cortex after the first task also reinstates NMDAR dependency. These results reveal cortico-hippocampal interactions supporting experience-dependent learning.
记忆形成的神经生物学主要在实验性的未经验动物中进行研究，但大多数学习都是在先前经验的背景下展开的。现在有相当多的证据表明，大脑对初始学习和后续学习的处理方式不同。在啮齿动物中，第一次情境性恐惧条件反射需要背侧海马体中的 NMDA 受体 (NMDAR) 激活，但随后对另一个情境的条件反射则不需要。这种转变可能是由于分子可塑性机制的变化，或者是学习第二个任务所需的信息发生了变化。为了阐明相关事件是如何被编码的，关键是要确定第一个任务的哪个方面涉及到 NMDA 受体非依赖性学习，以及维持这种状态的大脑区域。在这里，我们在大鼠中表明，海马体中 NMDA 受体的需求既不依赖于先前暴露于情境，也不单独依赖于足底电击，而是依赖于两个条件反射任务之间的程序相似性。重要的是，NMDA 受体非依赖性学习需要第一个任务的记忆仍然依赖于海马体。此外，在第一个任务后破坏前扣带皮层中的记忆维持也会重新建立 NMDA 受体的依赖性。这些结果揭示了支持经验依赖性学习的皮质-海马相互作用。
