美国霍华德·休斯医学院Jeffrey C. Magee课题组发现，内嗅皮层指导CA1表征中与学习有关的变化。相关论文于2022年11月2日在线发表于国际学术期刊《自然》。

研究人员记录了小鼠在线性跑步机上学习奖励地点时的海马CA1群体活动。生理和药理学证据表明，适应性的过度呈现需要行为时间尺度突触可塑性（BTSP）。BTSP已知是由树突电压信号驱动的，研究人员认为由来自内嗅皮层3（EC3）的输入启动。因此，通过光遗传学抑制EC3的活动，CA1的过度代表在很大程度上被消除。EC3神经元的记录显示了一种活动模式，它可以提供指示性信号，指导BTSP产生过度代表。

与这一功能相一致，观察表明，暴露在拥有突出的奖励预测线索的第二个环境中，EC3活动和CA1位置域密度在线索处比在奖励处更高。这些数据表明，海马区与学习有关的变化是由来自EC3的指示性信号指导的突触可塑性产生的，该信号似乎专门适应于环境中的行为相关特征。

据介绍，大脑活动中与学习有关的变化被认为是适应性行为的基础。例如，啮齿类动物对奖励地点的学习需要在海马中形成对该地点的一种过度代表。这种与学习有关的变化是如何发生的仍然是未知的。

附：英文原文

Title: Entorhinal cortex directs learning-related changes in CA1 representations

Author: Grienberger, Christine, Magee, Jeffrey C.

Issue&Volume: 2022-11-02

Abstract: Learning-related changes in brain activity are thought to underlie adaptive behaviours1,2. For instance, the learning of a reward site by rodents requires the development of an over-representation of that location in the hippocampus3,4,5,6. How this learning-related change occurs remains unknown. Here we recorded hippocampal CA1 population activity as mice learned a reward location on a linear treadmill. Physiological and pharmacological evidence suggests that the adaptive over-representation required behavioural timescale synaptic plasticity (BTSP)7. BTSP is known to be driven by dendritic voltage signals that we proposed were initiated by input from entorhinal cortex layer 3 (EC3). Accordingly, the CA1 over-representation was largely removed by optogenetic inhibition of EC3 activity. Recordings from EC3 neurons revealed an activity pattern that could provide an instructive signal directing BTSP to generate the over-representation. Consistent with this function, our observations show that exposure to a second environment possessing a prominent reward-predictive cue resulted in both EC3 activity and CA1 place field density that were more elevated at the cue than at the reward. These data indicate that learning-related changes in the hippocampus are produced by synaptic plasticity directed by an instructive signal from the EC3 that seems to be specifically adapted to the behaviourally relevant features of the environment.

DOI: 10.1038/s41586-022-05378-6

Source: https://www.nature.com/articles/s41586-022-05378-6