化学遗传学激活乳头体上核神经元增强大鼠学习记忆能力

Activating supramammillary nucleus by chemogenetics enhances learning and memory of rats

目的:探讨乳头体上核(SuM)在大鼠记忆巩固中的作用。方法:将rAAV2/9-CaMKIIa-EGFP注射到大鼠SuM核团,示踪其与海马之间的纤维联系,通过化学遗传学的方法激活SuM核团,即将rAAV2/9-hSyn-hM3D(Gq)-EGFP注射到大鼠SuM,3周后大鼠腹腔注射氯氮平-N-氧化物(CNO)激活SuM并检测大鼠在新物体识别实验和水迷宫实验中的表现,最后用免疫荧光染色验证SuM的激活情况。结果:SuM有顺行纤维投射到海马的齿状回(DG)、CA2区、CA3区。激活SuM,大鼠探究新物体的时间增加,更偏爱新物体;实验组大鼠平均逃避潜伏期、找到平台所用时间均低于对照组,实验组大鼠在原平台所在象限探索时间明显多于对照组。结论:SuM与海马存在广泛的纤维联系,激活SuM可以增强大鼠记忆巩固。

Objective:To investigate the effects of supramammillary nucleus(SuM)on consolidation of memory in rat.Methods:rAAV2/9-CaMKIla-EGFP was injected into SuM to mark the SuM neurons and their axons in hippocampus.The SuM was activated by chemogenetics method,i.e.rAAV2/9-hSyn-hM3D(Gq)-ECFP was injected into SuM.Three weeks later,rats were intraperitoneally injected with clozapine-N-oxide(CNO)to activate SuM,and the performance of rats in the novel object recognition test and Morris water maze was detected.Finally,the activation of SuM was verified by immunofluorescence staining.Results:SuM neurons project excitatory afferents to multiple areas of the hippocampus,such as dentate gyrus(DG),CA1,CA3.After activation of SuM,rats spent more time exploring new object and preferred new object.The average escape latency and the time to find the platform of the experimental group were lower than those of the control group,and the exploration time of the experimental group in the quadrant of the original platform was significantly longer than that of the control group.Conclusion:SuM neurons project excitatory afferents to multiple areas of the hippocampus.Activation of SuM can enhance memory consolidation in rat.