美国犹他大学James G. Heys研究组在研究中取得进展。他们发现内侧内嗅皮层（MEC）介导环境依赖性间隔计时行为。2024年6月14日，国际学术期刊《自然-神经科学》发表了这一成果。

研究人员表示，情节记忆需要对经验时间结构进行编码，并依赖于内侧颞叶大脑回路，包括MEC。最近的研究发现了内侧颞叶皮层的 "时间细胞"，这些细胞在完成时间间隔计时任务时会在特定时刻发射信号，并覆盖整个计时周期。有人推测，MEC时间细胞可提供外显记忆所需的时间信息，然而，目前仍不得而知它们是否表现出编码不同时间背景所需的学习动力。

为了探索MEC时间细胞的工作模式，研究人员开发了一种新的行为实验，要求小鼠区分时间情境。结合细胞分辨率钙成像方法，研究发现MEC时间细胞显示出与任务学习相关的神经活动。通过化学失活，研究发现MEC活动是学习情境依赖性时间间隔行为所必需的。

最后，研究发现了一种共同的电路机制，它可以驱动MEC中时间细胞和空间选择性神经元的序列活动。该研究表明，MEC时间细胞的时钟样发射可通过学习进行调节，从而跟踪通过经验产生的各种时间结构。

附：英文原文

Title: Medial entorhinal cortex mediates learning of context-dependent interval timing behavior

Author: Bigus, Erin R., Lee, Hyun-Woo, Bowler, John C., Shi, Jiani, Heys, James G.

Issue&Volume: 2024-06-14

Abstract: 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.

DOI: 10.1038/s41593-024-01683-7

Source: https://www.nature.com/articles/s41593-024-01683-7