外侧下丘脑食欲素能神经元-内侧内嗅皮层神经环路对空间记忆的调控作用  

Regulatory role of lateral hypothalamus hypocretin neurons-medial entorhinal cortex neural circuit in spatial memory in mice

作　　者：廖翊翔 郑孜艺[1] 程晓芳 文茹懿 夏建霞[1] 任栓成 何超[1] 胡志安[1] LIAO Yixiang;ZHENG Ziyi;CHENG Xiaofang;WEN Ruyi;XIA Jianxia;REN Shuancheng;HE Chao;HU Zhi’an(Department of Physiology,Collaborative Innovation Center for Brain Science,College of Basic Medical Sciences,Army Medical University(Third Military Medical University),Chongqing,400038;Department of Neurology,No.980 Hospital of PLA Joint Logistic Support Force,Shijiazhuang,Hebei Province,050499;Department of Emergency,No.953 Hospital of PLA Army,Shigatse,Tibet Autonomous Region,857000,China)

机构地区：[1]陆军军医大学(第三军医大学)基础医学院生理学教研室,脑与智能研究院,重庆400038 [2]联勤保障部队第九八〇医院神经内科,石家庄050499 [3]陆军第953医院急诊医学科,西藏日喀则857000

出　　处：《陆军军医大学学报》2023年第9期927-935,共9页Journal of Army Medical University

基　　金：国家自然科学基金面上项目(31970945);重庆市杰出青年科学基金项目(CSTB2022NSCQ-JQX2897)。

摘　　要：目的探究外侧下丘脑(lateral hypothalamus,LH)食欲素(hypocretin,Hcrt)能神经元-内侧内嗅皮层(medial entorhinal cortex,MEC)神经环路对空间记忆的调控作用。方法利用光纤记录技术,观察Hcrt能神经元在空间记忆中的活动模式。通过逆行神经示踪技术鉴定Hcrt能神经元与MEC浅层神经元的形态学联系特征。利用化学遗传学及光遗传学技术探究LH_(Hcrt)-MEC通路对空间记忆的影响。结果光纤记录实验发现LH的Hcrt能神经元在空间记忆相关行为中高水平激活(P<0.01)。逆行神经示踪实验发现Hcrt能神经元投射至空间记忆相关的MEC,LH投射至MEC的Hcrt能神经元在空间记忆中激活。化学遗传学抑制LH_(Hcrt)-MEC通路明显增加小鼠寻找食物正确空间位置的潜伏期(P<0.05)及小鼠寻得食物过程累计错误次数(P<0.05)。光遗传学激活LH_(Hcrt)-MEC通路显著降低小鼠早期寻找食物正确位置的潜伏期(P<0.05)。结论Hcrt能神经元参与空间记忆,LH投射至MEC浅层的Hcrt能神经元在空间记忆中激活,化学遗传学抑制LH_(Hcrt)-MEC通路损害空间记忆;光遗传学激活LH_(Hcrt)-MEC通路增强空间记忆。Objective To explore the regulatory effects of hypocretin(Hcrt)neurons in lateral hypothalamus(LH_(Hcrt))-medial entorhinal cortex(MEC)circuit on spatial memory.Methods The activity pattern of Hcrt neurons in spatial memory was recorded using in vivo fiber photometry.The morphological characteristics of connections between the Hcrt neurons and MEC neurons were identified with retrograde nerve tracer technique.Chemogenetics and optogenetics were subsequently adopted to confirm the effects of LH_(Hcrt)-MEC pathway on spatial memory.Results The optical fiber recording showed high levels of activation of Hcrt neurons during the spatial memory-related behaviors(P<0.01).The retrograde neural tracer test indicated that Hcrt neurons were projected to MEC which was associated with spatial memory,and those projected Hcrt neurons were confirmed being activated in spatial memory.Inhibition of the LH_(Hcrt)-MEC pathway by chemogenetics significantly prolonged the latency of mice to find the correct spatial location of food(P<0.05),and increased the number of errors in the process of finding food(P<0.05).However,photoactivation of the LH_(Hcrt)-MEC pathway by optogenetics remarkably reduced the latency of mice to find the food location at the initial training blocks(P<0.05).Conclusion Hcrt neurons are involved in spatial memory,and those Hcrt neurons projected from LH to the shallow layer of MEC are activated in spatial memory.Chemogenetic inhibition of the LH_(Hcrt)-MEC pathway impairs spatial memory,while optogenetic activation of this pathway enhances the function.

关 键 词：外侧下丘脑 食欲素 内侧内嗅皮层 空间记忆 

分 类 号：R-332[医药卫生] R338.27R338.64