痕迹性眨眼条件反射习得和巩固阶段海马中间神经元的放电活动变化  

Changes in hippocampal interneuronal activity during acquisition and consolidation of trace eyeblink conditioning in mice

作　　者：杨丹阳[1] 张维维[2] YANG Danyang;ZHANG Weiwei(Department of Diagnosis,School of Clinical Medicine,School of Basic Medicine,Sichuan College of Traditional Chinese Medicine,Mianyang,Sichuan Province,621000,China;Department of Physiology,School of Basic Medicine,Sichuan College of Traditional Chinese Medicine,Mianyang,Sichuan Province,621000,China)

机构地区：[1]四川中医药高等专科学校临床医学院诊断学教研室,四川绵阳621000 [2]四川中医药高等专科学校医学基础部生理学教研室,四川绵阳621000

出　　处：《陆军军医大学学报》2024年第16期1874-1881,共8页Journal of Army Medical University

基　　金：四川省科技计划项目(22NSFSC0572)。

摘　　要：目的研究小鼠背侧海马中间神经元在联合型记忆习得和巩固2个阶段的放电活动变化及其特征。方法以痕迹性眨眼条件反射(trace eyeblink conditioning,tEBC)作为联合型记忆行为模型,将18只野生型C57BL/6小鼠(雄性,10~12周龄,体质量22~25 g)通过简单随机抽样分为配对组(n=9)和假配对组(n=9)。配对组每天接受配对给予的条件刺激(conditioned stimulus,CS)和非条件刺激(unconditioned stimulus,US),二者的配对关系为CS结束后250 ms给予US。假配对组每天接受同样数量的CS和US,但二者不存在时间上的配对关系。连续训练4 d,配对组小鼠建立tEBC,表现出条件眨眼反应(conditioned eyeblink response,CR)。在每天的训练过程中和训练后1.5 h,利用微电极阵列在体记录小鼠背侧海马神经元的放电活动。根据神经元的峰电位发放频率和峰电位谷-峰波宽鉴定出中间神经元(n=105),并分析其在训练期间和训练后慢波睡眠期间的放电活动变化。结果①在CR习得训练早期(第1、2天),CS能够诱发背侧海马中间神经元出现显著增强的发放活动(P<0.05);训练后慢波睡眠期间尖波涟漪波(sharp wave ripple,SWR)振荡发生时,配对组小鼠背侧海马中间神经元发放频率显著低于假配对组(P<0.05)。②在CR习得训练后期(第3、4天),与假配对组比较,配对组CS诱发的背侧海马中间神经元放电活动增强不明显;2组小鼠背侧海马中间神经元在训练后慢波睡眠期SWR振荡发生时的发放频率差异无统计学意义。结论背侧海马中间神经元在联合型记忆的习得和巩固阶段会展现出不同的放电变化。Objective To investigate the changes and features of firing activities of interneurons in dorsal hippocampus during the acquisition and consolidation of associative memory.Methods Trace eyeblink conditioning(tEBC)was utilized as a behavioral model of associative memory.A total of 18 wild-type C57BL/6 mice(male,10~12 weeks old,weighing 22~25 g)were randomly divided into a paired group(n=9)and an unpaired group(n=9).Paired presentations of conditioned stimulus(CS)and unconditioned stimulus(US)were utilized to train these mice.The mice from the paired group were given US training in 250 ms after CS training,and those from the unpaired group received similar doses of CS and US training,but with no paired relationship in time.After 4 consecutive days’training,the mice of the paired group acquired tEBC,manifesting conditioned eyeblink responses(CR).Tetrode arrays were applied to record neuronal activity in dorsal hippocampus during both tEBC training epoch and the 1.5 h epoch after training.The putative interneurons(n=105)were identified according to their firing rate and spike width from trough to peak.Specific changes in hippocampal interneurons activity during tEBC training and post-training slow wave sleep were analyzed respectively.Results①At the early stage of CR acquisition(the 1 st and 2 nd days),CS could evoke significantly greater activity of dorsal hippocampal interneurons in the paired group(P<0.05).During sharp wave ripples(SWR)in the post-training slow wave sleep,the firing rate of dorsal hippocampal interneurons was significantly lower in the paired group than the unpaired group(P<0.05).②At the late stage of CR acquisition(the 3 rd and 4 th days),no significant differences in CS evoked activity of dorsal hippocampal interneurons were observed between the paired group and unpaired group,neither in the firing rate of dorsal hippocampal interneurons during SWR in the post-training slow wave sleep between the 2 groups.Conclusion The dorsal hippocampal interneurons show opposite changes in firing activi

关 键 词：海马 中间神经元 眨眼条件反射 慢波睡眠 尖波涟漪波 

分 类 号：R338.26[医药卫生—人体生理学] R338.61[医药卫生—基础医学] R338.8