Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong.
City University of Hong Kong Shenzhen Research Institute, 518057 Shenzhen, China.
Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6397-6406. doi: 10.1073/pnas.1816833116. Epub 2019 Mar 8.
Memory is stored in neural networks via changes in synaptic strength mediated in part by NMDA receptor (NMDAR)-dependent long-term potentiation (LTP). Here we show that a cholecystokinin (CCK)-B receptor (CCKBR) antagonist blocks high-frequency stimulation-induced neocortical LTP, whereas local infusion of CCK induces LTP. CCK mice lacked neocortical LTP and showed deficits in a cue-cue associative learning paradigm; and administration of CCK rescued associative learning deficits. High-frequency stimulation-induced neocortical LTP was completely blocked by either the NMDAR antagonist or the CCKBR antagonist, while application of either NMDA or CCK induced LTP after low-frequency stimulation. In the presence of CCK, LTP was still induced even after blockade of NMDARs. Local application of NMDA induced the release of CCK in the neocortex. These findings suggest that NMDARs control the release of CCK, which enables neocortical LTP and the formation of cue-cue associative memory.
记忆是通过神经递质突触强度的变化存储在神经网络中的，这种变化部分由 NMDA 受体（NMDAR）依赖性长时程增强（LTP）介导。在这里，我们发现胆囊收缩素（CCK）-B 受体（CCKBR）拮抗剂可阻断高频刺激诱导的新皮层 LTP，而局部输注 CCK 可诱导 LTP。CCK 敲除小鼠缺乏新皮层 LTP，并且在线索-线索联想学习范式中表现出缺陷；而 CCK 的给药可挽救联想学习缺陷。NMDAR 拮抗剂或 CCKBR 拮抗剂均可完全阻断高频刺激诱导的新皮层 LTP，而 NMDA 或 CCK 的应用可在低频刺激后诱导 LTP。在 CCK 存在的情况下，即使阻断 NMDAR 后仍可诱导 LTP。局部应用 NMDA 可诱导新皮层中 CCK 的释放。这些发现表明，NMDAR 控制 CCK 的释放，从而使新皮层 LTP 和线索-线索联想记忆的形成成为可能。
