The Contribution of AMPA and NMDA Receptors to Persistent Firing in the Dorsolateral Prefrontal Cortex in Working Memory
The Contribution of AMPA and NMDA Receptors to Persistent Firing in the Dorsolateral Prefrontal Cortex in Working Memory
复制标题
DOI：
10.1523/jneurosci.2121-19.2020
复制
发表时间：
2020-03-18
影响因子：
5.3
通讯作者：
Roelfsema, Pieter R.
中科院分区：
文献类型：
--
作者：
van Vugt, Bram;van Kerkoerle, Timo;Roelfsema, Pieter R.
许多任务要求信息在用于指导行为之前保持在线几秒钟。这些信息被保存在工作记忆中，作为对记忆信息进行编码的神经元的持续放电。负责持续活动的神经机制尚未得到很好的理解。理论将重要作用归因于离子型谷氨酸受体，并且已经表明NMDAR对于持续放电特别重要，因为它们表现出长的时间常数。离子迁移性AMPAR具有较短的时间常数，并被认为在工作记忆中起较小的作用。在这里，我们比较的贡献AM PARs和NMDARs持续放电的dlPFC的雄性猕猴执行延迟扫视记忆的空间位置。我们使用离子导入法排出少量的谷氨酸受体拮抗剂，目的是扰乱，但不是取消，神经元的活动。我们发现AMPAR和NMDAR都有助于持续的活动。阻断剂的NMDARs减少持续放电与记忆的神经元的首选空间位置，但相对较小的影响，代表的antipreferred位置。因此，他们减少了持续射击所传递的关于记忆位置的信息。相比之下，AMPAR阻断剂减少了由首选和反首选位置的记忆引起的活动，对持续活动所传达的信息的影响较小。我们的研究结果为AMPAR和NMDAR在工作记忆任务中对持续活动的贡献提供了新的见解。
Many tasks demand that information is kept online for a few seconds before it is used to guide behavior. The information is kept in working memory as the persistent firing of neurons encoding the memorized information. The neural mechanisms responsible for persistent activity are not yet well understood. Theories attribute an important role to ionotropic glutamate receptors, and it has been suggested that NMDARs are particularly important for persistent firing because they exhibit long time constants. lonotropic AMPARs have shorter time constants and have been suggested to play a smaller role in working memory. Here we compared the contribution of AM PARs and NMDARs to persistent firing in the dlPFC of male macaque monkeys performing a delayed saccade to a memorized spatial location. We used iontophoresis to eject small amounts of glutamate receptor antagonists, aiming to perturb, but not abolish, neuronal activity. We found that both AMPARs and NMDARs contributed to persistent activity. Blockers of the NMDARs decreased persistent firing associated with the memory of the neuron's preferred spatial location but had comparatively little effect on the representation of the antipreferred location. They therefore decreased the information conveyed by persistent firing about the memorized location. In contrast, AMPAR blockers decreased activity elicited by the memory of both the preferred and antipreferred location, with a smaller effect on the information conveyed by persistent activity. Our results provide new insights into the contribution of AMPARs and NMDARs to persistent activity during working memory tasks.