丘脑连接核通过内侧内嗅皮层调控空间记忆初步研究

Thalamic nucleus reuniens regulates spatial memory via medial entorhinal cortex:a preliminary study

目的 初步探究丘脑连接核(thalamic nucleus reuniens, RE)调控内侧内嗅皮层(medial entorhinal cortex, MEC)相关的空间记忆及机制。方法 Retrobeads介导的逆行示踪技术结合顺行示踪技术鉴定RE与MEC脑区之间的形态学联系。利用光纤记录技术,记录并分析小鼠在空旷场探索时投射至MEC的RE神经元的活动特征。采用化学遗传学抑制RE-MEC通路探究对空间记忆的影响。结果 逆行与顺行示踪实验验证了RE发出神经纤维投射至MEC,且主要分布在浅层。光纤记录实验发现投射至MEC的RE神经元在小鼠在站立、抬头行为时活动增强,而在静止和理毛时活动减弱(P<0.01),且这群神经元的钙活动与小鼠运动速度呈正相关(R^(2)=0.077 3,P<0.001)。与对照组比较,化学遗传学抑制RE-MEC通路明显增加处理组小鼠在空旷场中探索的路程(P<0.01),而对中央区的停留时间、刻板理毛行为次数无影响。结论 RE-MEC通路在空间探索行为期间激活,参与空间学习记忆;抑制RE-MEC通路损害小鼠的空间记忆,延长小鼠对新环境空间信息进行表征的探索距离,而对小鼠的情绪无影响。

Objective To preliminarily investigate the role of thalamic nucleus reuniens(RE)on medial entorhinal cortex(MEC)-related spatial memory and its mechanism.Methods Retrobeads-mediated retrograde tracing and anterograde tracing were used to identify the morphological connections between RE and MEC brain regions.Then in vivo fiber photometry was used to record and analyze the activities of RE MEC-projecting neurons when mice were exploring in the open field.Chemical genetics was utilized to explore the effects of RE-MEC pathway inhibition on spatial memory.Results Retrograde and anterograde tracing confirmed that RE sent neuronal fibers to MEC,which were mainly distributed in the superficial layers.Optical fiber recording showed that the activities of RE MEC-projecting neurons were increased when the mice were rearing and looking up,but were decreased when the mice were stationary and grooming(R 2=0.0773,P<0.01).And the calcium signal of these neurons was positively correlated with movement speed.Compared with the control group,chemogenetic inhibition of the RE-MEC pathway significantly prolonged the exploration distance of the mice in the treatment group in the open field(P<0.01),but showed no effects on the center time,rearing time,number of head ups and number of grooming.Conclusion RE-MEC pathway is activated during spatial exploratory behaviors and participates in spatial learning and memory.Chemogenetic inhibition of RE-MEC pathway impairs spatial memory and extends the exploration distance to represent the spatial information of novel environment,and has no effects on emotions.