Interdepartmental PhD Program in Neuroscience, University of Utah, Salt Lake City, UT, USA.
Department of Neurobiology, University of Utah, Salt Lake City, UT, USA.
Nat Neurosci. 2024 Aug;27(8):1587-1598. doi: 10.1038/s41593-024-01683-7. Epub 2024 Jun 14.
Episodic memory requires encoding the temporal structure of experience and relies on brain circuits in the medial temporal lobe, including the medial entorhinal cortex (MEC). Recent studies have identified MEC 'time cells', which fire at specific moments during interval timing tasks, collectively tiling the entire timing period. It has been hypothesized that MEC time cells could provide temporal information necessary for episodic memories, yet it remains unknown whether they display learning dynamics required for encoding different temporal contexts. To explore this, we developed a new behavioral paradigm requiring mice to distinguish temporal contexts. Combined with methods for cellular resolution calcium imaging, we found that MEC time cells display context-dependent neural activity that emerges with task learning. Through chemogenetic inactivation we found that MEC activity is necessary for learning of context-dependent interval timing behavior. Finally, we found evidence of a common circuit mechanism that could drive sequential activity of both time cells and spatially selective neurons in MEC. Our work suggests that the clock-like firing of MEC time cells can be modulated by learning, allowing the tracking of various temporal structures that emerge through experience.
情景记忆需要对经验的时间结构进行编码，并且依赖于包括内侧内嗅皮层（MEC）在内的内侧颞叶回路。最近的研究已经确定了 MEC 的“时间细胞”，它们在间隔计时任务中在特定时刻发射，集体平铺整个计时周期。有人假设 MEC 时间细胞可以提供情景记忆所需的时间信息，但尚不清楚它们是否显示出编码不同时间上下文所需的学习动态。为了探索这一点，我们开发了一种需要小鼠区分时间上下文的新行为范式。结合用于细胞分辨率钙成像的方法，我们发现 MEC 时间细胞显示出与任务学习一起出现的与上下文相关的神经活动。通过化学遗传失活，我们发现 MEC 活性对于学习与上下文相关的间隔计时行为是必要的。最后，我们发现了一种共同的电路机制的证据，该机制可以驱动 MEC 中时间细胞和空间选择性神经元的顺序活动。我们的工作表明，MEC 时间细胞的类似时钟的发射可以通过学习来调节，从而允许跟踪通过经验产生的各种时间结构。
