联合型运动学习过程中小鼠内侧前额叶皮层神经元放电活动研究  

Neuronal discharge activity in mouse medial prefrontal cortex during associative motor learning

作　　者：胡昱博 章利彬 陈浩[3] 熊雁[1] HU Yubo;ZHANG Libin;CHEN Hao;XIONG Yan(Department of Orthopaedics,Daping Hospital,Army Medical University(Third Military Medical University),Chongqing,400042;Department of General Surgery,No.948 Hospital of PLA,Wusu,Xinjiang Uygur Autonomous Region,833000;Experimental Center of Basic Medicine,College of Basic Medical Sciences,Army Medical University(Third Military Medical University),Chongqing,400038,China)

机构地区：[1]陆军军医大学(第三军医大学)大坪医院骨科,重庆400042 [2]中国人民解放军第948医院普通外科,新疆维吾尔自治区乌苏833000 [3]陆军军医大学(第三军医大学)基础医学院基础医学教学实验中心,重庆400038

出　　处：《第三军医大学学报》2021年第24期2618-2624,共7页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81871039)。

摘　　要：目的研究联合型运动学习过程中小鼠内侧前额叶皮层(medial prefrontal cortex,mPFC)不同类型神经元放电活动变化的规律及其与学习行为的相关性。方法以痕迹性眨眼条件反射(trace eyeblink conditioning,tEBC)作为联合型运动学习的行为模型。以150 ms脉冲蓝色LED光作为条件刺激(conditioned stimulus,CS),100 ms角膜吹气作为非条件刺激(unconditioned stimulus,US),进行每日100次的CS-US配对训练。连续5 d,训练小鼠(n=4)建立tEBC。在此过程中,使用钨丝tetrode电极记录小鼠mPFC神经元放电活动。根据神经元放电的频率和峰电位谷-峰波宽,将mPFC神经元区分为假定的锥体细胞(n=174)和中间神经元(n=40),并分析两类神经元活动在tEBC建立早期和后期与条件眨眼反应(conditioned eyeblink responses,CR)行为的相关性。结果通过5 d CS-US配对训练,小鼠CR发生率从训练第1天的(38.1±8.2)%上升到第5天的(66.7±10.0)%(P<0.001)。统计学分析显示,相较于CR习得早期,CR习得后期CS所诱发的锥体细胞放电活动显著降低(P<0.05)。与此相适应,CR习得后期CS诱发的中间神经元放电活动显著增高(P<0.05),表现为CS诱发增强型放电的中间神经元比例显著增高(早期:25.0%;后期:66.7%,P<0.05)。此外,锥体细胞在CR出现和无CR出现时的CS诱发放电活动无显著区别(P>0.05),而中间神经元在CR出现时CS诱发放电活动则显著更高(P<0.05)。结论在联合型运动学习过程中,小鼠mPFC锥体细胞和中间神经元的放电活动随学习会发生相反的变化,提示它们可能以不同方式参与联合型运动学习。中间神经元放电活动与CR出现更为相关。Objective To investigate the discharge profiles of different types of neurons in the medial prefrontal cortex(mPFC) during associative motor learning and their correlation with learning behaviors.Methods Trace eyeblink conditioning(tEBC) was used as the behavioral model of associative motor learning.Freely-moving mice(n=4) were trained to acquire tEBC for 5 consecutive days.During daily tEBC training,the mice were received 100 paired presentations of the conditioned stimulus(CS,150-ms blue LED pulse) and unconditioned stimulus(US,100-ms corneal airpuff).Tungsten tetrodes were utilized to record the discharge activity of mPFC neurons.The mPFC neurons were categorized into putative pyramidal cells(n=174) and putative interneurons(n=40) according to the discharge rate and width of the mean spike waveform from trough to peak for each neuron.The correlation between the activity of distinct mPFC neurons and the performance of conditioned eyeblink responses(CR) was analyzed in either the early-or the late-learning stage.Results After 5 days’ CS-US paired training,the mice exhibited increased CR incidence from(38.1±8.2)% on the 1 st day to(66.7±10.0)% on the 5 th day(P<0.001).The statistical analysis revealed that the CS-evoked discharge activity of putative mPFC pyramidal cells at the late-leaning stage was significantly weaker than the early-learning stage(P<0.05).In contrast,the CS-evoked discharge activity of putative interneurons at the late-learning stage was significantly greater than that at the early-learning stage(P<0.05).Consistent with this,the proportion of CS-evoked increased firing interneurons was significantly greater at the late-learning stage(66.7%,14/21) than the early-learning stage(25.0%,4/16,P<0.05).Moreover,there was no significant difference in the CS-evoked activity of mPFC pyramidal cells between the CR and the non-CR states(P>0.05),whereas the CS-evoked activity of mPFC interneurons in the presence of CRs was stronger than in the lack of CRs(P<0.05).Conclusion During the acquisition of tEB

关 键 词：条件反射 眨眼 运动性学习 内侧前额叶皮层 多通道记录 

分 类 号：R338.25[医药卫生—人体生理学] R338.64[医药卫生—基础医学]