Cholecystokinin from the Entorhinal Cortex Enables Long-term Potentiation in the Auditory Cortex
Xiao LiXi ChenZicong ZhangQing LiuZhi-Jian ZhangXiao-Bin HeWenjian SunJingyu FengYin Ting WongHemin FengKelvin WongKai YuXue-Jiao ZhengNan ZhangCaroline Ling HeAi-Lain Tan HeLing-Li HuMin-Yan DangHaitao WangWenxi YeChun-Hua LiuYi Ping GuoFuqing XuJufang He
Department of Biomedical Sciences,City University of Hong KongWuhan Institute of Physics and Mathematics,Chinese Academy of SciencesCity University of Hong Kong Shenzhen Research InstituteSchool of Life Science and Technology,Harbin Institute of TechnologyGuangzhou Institute of Biomedicine and Health,Chinese Academy of Sciences
摘要：Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin（CCK）. Local infusion of CCK in the auditory cortex ofanesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCKB antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCKB antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex. In the second part of the experiment, the bilaterally electrode-implanted rat was trained to retrieve water-reward from either the leftmost or the rightmost hole depending on which hemisphere of the auditory cortex stimulation was triggered after it initiated the trial. After the stimulation site of one hemisphere was infused with CCK, a previously irrelevant light stimulus was then paired with the electrical stimulation of the infused hemisphere for multiple sessions in the anesthetized rat. The auditory cortex neurons responded to the light stimulus in both anesthetized and behavioral conditions. All rats approached to the "engineered" hole after they triggered light stimulus instead of electrical stimulation of the auditory cortex one week after the first conditioning. The behavioral experiment revealed that the artificially memory was transferred to the behavioral action, providing a scientific foundation for "memory implantation".