美国加州大学洛杉矶分校Peyman Golshani等研究人员合作发现，不稳定的工作记忆表征会随着练习而固化。相关论文于2024年5月15日在线发表在《自然》杂志上。

研究人员表示，工作记忆是在短时间内对信息进行短暂保持和操作的过程，对大多数认知功能至关重要。然而，工作记忆神经元表征在群体水平上的长期生成和演化机制仍不清楚。

为了确定这些机制，研究人员训练了头部固定的小鼠执行嗅觉延迟联想任务。在延迟晚期和选择期对次级运动神经元进行光遗传学抑制会严重影响小鼠的任务表现。对次级运动皮层（M2）、回脾皮层（RSA）和初级运动皮层（M1）的大量神经元群进行的介观钙成像显示，在小鼠学习任务时，M2中出现了许多晚延迟时相选择性神经元。随着小鼠成为专家，工作记忆晚延时解码准确性在M2中大幅提高，而在M1或RSA中则没有提高。

在早期专家阶段，延时晚期的工作记忆表征会在不同天内漂移，而刺激和选择表征则趋于稳定。与单平面2/3层（L2/3）成像不同的是，对多达73307个M2神经元（包括浅层L5神经元）同时进行的容积钙成像也显示，随着持续练习，延迟后期工作记忆表征趋于稳定。因此，对工作记忆表现至关重要的延迟和选择相关活动在学习过程中会发生漂移，只有在几天的专家表现后才会稳定下来。

附：英文原文

Title: Volatile working memory representations crystallize with practice

Author: Bellafard, Arash, Namvar, Ghazal, Kao, Jonathan C., Vaziri, Alipasha, Golshani, Peyman

Issue&Volume: 2024-05-15

Abstract: Working memory, the process through which information is transiently maintained and manipulated over a brief period, is essential for most cognitive functions1,2,3,4. However, the mechanisms underlying the generation and evolution of working-memory neuronal representations at the population level over long timescales remain unclear. Here, to identify these mechanisms, we trained head-fixed mice to perform an olfactory delayed-association task in which the mice made decisions depending on the sequential identity of two odours separated by a 5s delay. Optogenetic inhibition of secondary motor neurons during the late-delay and choice epochs strongly impaired the task performance of the mice. Mesoscopic calcium imaging of large neuronal populations of the secondary motor cortex (M2), retrosplenial cortex (RSA) and primary motor cortex (M1) showed that many late-delay-epoch-selective neurons emerged in M2 as the mice learned the task. Working-memory late-delay decoding accuracy substantially improved in the M2, but not in the M1 or RSA, as the mice became experts. During the early expert phase, working-memory representations during the late-delay epoch drifted across days, while the stimulus and choice representations stabilized. In contrast to single-plane layer 2/3 (L2/3) imaging, simultaneous volumetric calcium imaging of up to 73,307 M2 neurons, which included superficial L5 neurons, also revealed stabilization of late-delay working-memory representations with continued practice. Thus, delay- and choice-related activities that are essential for working-memory performance drift during learning and stabilize only after several days of expert performance.

DOI: 10.1038/s41586-024-07425-w

Source: https://www.nature.com/articles/s41586-024-07425-w