Cholecystokinin release triggered by NMDA receptors produces LTP and sound-sound associative memory

Xi Chen, Xiao Li, Yin Ting Wong, Xuejiao Zheng, Haitao Wang, Yujie Peng, Hemin Feng, Jingyu Feng, Joewel T. Baibado, Robert Jesky, Zhedi Wang, Hui Xie, Wenjian Sun, Zicong Zhang, Xu Zhang, Ling He, Nan Zhang, Zhijian Zhang, Peng Tang, Junfeng SuLing Li Hu, Qing Liu, Xiaobin He, Ailian Tan, Xia Sun, Min Li, Kelvin Wong, Xiaoyu Wang, Hon Yeung Cheung, Daisy Kwok Yan Shum, Kin Lam YUNG, Ying Shing Chan, Micky Tortorella, Yiping Guo, Fuqiang Xu, Jufang He*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

37 Citations (Scopus)


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. Highfrequency 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 lowfrequency 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.

Original languageEnglish
Pages (from-to)6397-6406
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
Early online date8 Mar 2019
Publication statusPublished - 26 Mar 2019

Scopus Subject Areas

  • General

User-Defined Keywords

  • Cholecystokinin
  • Entorhinal cortex
  • Long-term potentiation
  • Memory
  • NMDA receptor


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