Memory recall involves a transient break in excitatory-inhibitory balance.
Memory recall involves a transient break in excitatory-inhibitory balance.
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DOI：
10.7554/elife.70071
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发表时间：
2021-10-08
期刊：
影响因子：
7.7
通讯作者：
Barron HC
中科院分区：
文献类型：
--
作者：
Koolschijn RS;Shpektor A;Clarke WT;Ip IB;Dupret D;Emir UE;Barron HC
大脑有一种非凡的能力来获取和储存记忆，这些记忆可以在以后有选择地回忆起来。这些过程由海马体支持，海马体被认为通过恢复存储在分布的新皮层回路中的信息来索引记忆回忆。然而，支持这种相互作用的机制仍不清楚。在这里，在人类中，我们表明，从一对联营公司的视觉线索的回忆是伴随着短暂的增加谷氨酸和GABA之间的比例在视觉皮层。此外，这些兴奋-抑制波动是由海马体的活动预测的。这些数据表明，海马门记忆回忆索引信息存储在新皮层电路使用去抑制机制。记忆由大脑中分布的神经元群存储，单个神经元对多种记忆有贡献。在大脑的一个叫做新皮层的部分，记忆通过兴奋和抑制活动之间的平衡保持在一种沉默的状态。这是为了防止他们被传入的信息所干扰。当一段记忆被唤起时，大脑中一个叫做海马体的区域被认为会指示新皮层激活相应的神经元网络。但是海马体和新皮层是如何协调它们的活动来“打开”和“关闭”记忆的还不清楚。答案可能在于新皮层的神经元由两大类组成：兴奋性神经元和抑制性神经元。兴奋性神经元增加其他神经元的活动。它们通过释放一种叫做谷氨酸的化学物质来达到这个目的。抑制性神经元通过释放一种叫做GABA的化学物质来减少其他神经元的活动。Koolyjn，Shpektor等人假设海马通过改变新皮层中兴奋性和抑制性活动的平衡来激活记忆。为了验证这一想法，Koolyjn，Shpektor等人邀请健康的志愿者探索虚拟现实环境。志愿者们了解到，环境中的特定声音可以预测特定视觉模式的出现。第二天，志愿者们回到环境中，再次观察这些图案。在每个图案之后，他们被邀请打开一个虚拟盒子。志愿者了解到，有些模式会导致虚拟盒子中的钱，而其他模式则不会。最后，在第三天，志愿者们再次聆听第一天的声音，这次是躺在大脑扫描仪中。志愿者的任务是推断每一种声音是否会带来金钱。由于声音从未与虚拟盒子的内容直接配对，志愿者必须通过回忆相关的视觉模式来解决任务。当他们这样做时，大脑扫描仪测量了他们的整体大脑活动。它还通过测量谷氨酸和GABA来评估新皮层视觉区域兴奋性和抑制性活动的相对水平。结果显示，当志愿者回忆起视觉线索时，海马体和视觉新皮层的活动都增加了。此外，视觉新皮层中谷氨酸与GABA的比例也增加，这是由海马中的活性预测的。这表明海马通过暂时增加兴奋性活动来重新激活存储在新皮层中的记忆，以将记忆从抑制性控制中释放出来。兴奋和抑制平衡的紊乱发生在各种神经精神障碍中，包括精神分裂症、自闭症、癫痫和图雷特综合征。海马体受损会导致失忆。目前的研究结果表明，当海马体和新皮层之间的相互作用出错时，记忆可能会变得不可访问-或者可能会被不适当地激活。未来的研究可以在临床人群中测试这种可能性。
The brain has a remarkable capacity to acquire and store memories that can later be selectively recalled. These processes are supported by the hippocampus which is thought to index memory recall by reinstating information stored across distributed neocortical circuits. However, the mechanism that supports this interaction remains unclear. Here, in humans, we show that recall of a visual cue from a paired associate is accompanied by a transient increase in the ratio between glutamate and GABA in visual cortex. Moreover, these excitatory-inhibitory fluctuations are predicted by activity in the hippocampus. These data suggest the hippocampus gates memory recall by indexing information stored across neocortical circuits using a disinhibitory mechanism. Memories are stored by distributed groups of neurons in the brain, with individual neurons contributing to multiple memories. In a part of the brain called the neocortex, memories are held in a silent state through a balance between excitatory and inhibitory activity. This is to prevent them from being disrupted by incoming information. When a memory is recalled, an area of the brain called the hippocampus is thought to instruct the neocortex to activate the appropriate neuronal network. But how the hippocampus and neocortex coordinate their activity to switch memories ‘on’ and ‘off’ is unclear. The answer may lie in the fact that neurons in the neocortex consist of two broad types: excitatory and inhibitory. Excitatory neurons increase the activity of other neurons. They do this by releasing a chemical called glutamate. Inhibitory neurons reduce the activity of other neurons, by releasing a chemical called GABA. Koolschijn, Shpektor et al. hypothesized that the hippocampus activates memories by changing the balance of excitatory and inhibitory activity in neocortex. To test this idea, Koolschijn, Shpektor et al. invited healthy volunteers to explore a virtual reality environment. The volunteers learned that specific sounds in the environment predicted the appearance of particular visual patterns. The next day, the volunteers returned to the environment and viewed these patterns again. After each pattern, they were invited to open a virtual box. Volunteers learned that some patterns led to money in the virtual box, while other patterns did not. Finally, on day three, the volunteers listened to the sounds from day one again, this time while lying in a brain scanner. The volunteers’ task was to infer whether each of the sounds would lead to money. Given that the sounds were never directly paired with the content of the virtual box, the volunteers had to solve the task by recalling the associated visual patterns. As they did so, the brain scanner measured their overall brain activity. It also assessed the relative levels of excitatory and inhibitory activity in visual areas of the neocortex, by measuring glutamate and GABA. The results revealed that as the volunteers recalled the visual cues, activity in both the hippocampus and the visual neocortex increased. Moreover, the ratio of glutamate to GABA in visual neocortex also increased which was predicted by activity in the hippocampus. This suggests that the hippocampus reactivates memories stored in neocortex by temporarily increasing excitatory activity to release memories from inhibitory control. Disturbances in the balance of excitation and inhibition occur in various neuropsychiatric disorders, including schizophrenia, autism, epilepsy and Tourette’s syndrome. Damage to the hippocampus is known to cause amnesia. The current findings suggest that memories may become inaccessible – or may be activated inappropriately – when the interaction between the hippocampus and neocortex goes awry. Future studies could test this possibility in clinical populations.