Sainsbury Wellcome Centre, University College London, London, UK.
Biozentrum, University of Basel, Basel, Switzerland.
Nature. 2022 Aug;608(7922):381-389. doi: 10.1038/s41586-022-05014-3. Epub 2022 Jul 27.
Working memory-the brain's ability to internalize information and use it flexibly to guide behaviour-is an essential component of cognition. Although activity related to working memory has been observed in several brain regions, how neural populations actually represent working memory and the mechanisms by which this activity is maintained remain unclear. Here we describe the neural implementation of visual working memory in mice alternating between a delayed non-match-to-sample task and a simple discrimination task that does not require working memory but has identical stimulus, movement and reward statistics. Transient optogenetic inactivations revealed that distributed areas of the neocortex were required selectively for the maintenance of working memory. Population activity in visual area AM and premotor area M2 during the delay period was dominated by orderly low-dimensional dynamics that were, however, independent of working memory. Instead, working memory representations were embedded in high-dimensional population activity, present in both cortical areas, persisted throughout the inter-stimulus delay period, and predicted behavioural responses during the working memory task. To test whether the distributed nature of working memory was dependent on reciprocal interactions between cortical regions, we silenced one cortical area (AM or M2) while recording the feedback it received from the other. Transient inactivation of either area led to the selective disruption of inter-areal communication of working memory. Therefore, reciprocally interconnected cortical areas maintain bound high-dimensional representations of working memory.
工作记忆——大脑内化信息并灵活运用信息来指导行为的能力——是认知的一个重要组成部分。尽管已经在几个脑区观察到与工作记忆相关的活动，但神经群体如何实际表示工作记忆以及这种活动是如何维持的仍然不清楚。在这里，我们描述了在延迟非匹配样本任务和简单的辨别任务之间交替进行的小鼠视觉工作记忆的神经实现，该任务不需要工作记忆，但具有相同的刺激、运动和奖励统计数据。短暂的光遗传学失活显示，新皮层的分布式区域选择性地需要维持工作记忆。在延迟期间，视觉区域 AM 和运动前区域 M2 的群体活动主要由有序的低维动力学主导，但与工作记忆无关。相反，工作记忆的表示嵌入在高维群体活动中，存在于两个皮质区域中，在整个刺激间延迟期间持续存在，并预测工作记忆任务期间的行为反应。为了测试工作记忆的分布式性质是否取决于皮质区域之间的相互作用，我们在记录另一个区域从它那里接收到的反馈的同时沉默一个皮质区域（AM 或 M2）。任一个区域的短暂失活都会导致工作记忆的区域间通信选择性中断。因此，相互连接的皮质区域维持着工作记忆的绑定高维表示。
