Assessment of operant learning and memory in mice born through ICSI.
Assessment of operant learning and memory in mice born through ICSI.
复制标题
DOI：
10.1093/humrep/deaa167
复制
发表时间：
2020-08
影响因子：
6.1
通讯作者：
Matthew Lewon;Yue Wang;Christina Peters;Matthew Peterson;Huili Zheng;Zhuqing Wang;L. Hayes;Wei Yan
中科院分区：
文献类型：
--
作者：
Matthew Lewon;Yue Wang;Christina Peters;Matthew Peterson;Huili Zheng;Zhuqing Wang;L. Hayes;Wei Yan
研究问题通过ICSI出生的小鼠和自然受孕的对照(CTL)小鼠在操作性学习和记忆方面是否存在差异？内容提要ICSI女性相对于CTL女性在获得奖赏学习方面表现出缺陷，ICSI男性相对于CTL男性表现出辨别学习和记忆缺陷。已知的一些人类结局研究表明，ICSI可能与某些认知障碍的风险增加有关，但在两项针对ICSI小鼠模型的行为研究中，只有一项报告了ICSI和CTL雌性之间的差异。到目前为止，还没有研究调查ICSI小鼠的联想学习。研究设计比较了36只ICSI小鼠(18只雄性，18只雌性)和37只CTL小鼠(19只雄性，18只雌性)3-6月龄的可操作性学习程序，以评估新行为的获得、辨别学习和记忆。总共有16只ICSI小鼠(9只雄性，7只雌性)和17只CTL小鼠(10只雄性，7只雌性)在12个月大时(初始训练结束后6个月)接受了跟踪辨别学习和记忆评估，以评估学习成绩的保持和重新获得。参与者/材料、环境、方法小鼠每天在实验室接受操作式学习，其中所有刺激事件和反应的记录都是自动进行的。食物奖励是在不同的加固条件下做出反应的，不同的程序有所不同。受试者接受了一系列的鼻戳习得训练、辨别训练和延迟不匹配位置记忆程序。数据分析采用混合重复测量方差分析，其中受试者之间的因素是组(ICSI与CTL)，受试者内的因素是重复暴露于学习过程(即会话)。主要结果和机会在所有小鼠(即雄性和雌性小鼠的总和)之间的比较中，CTL小鼠在反应获得(P=0.03)、辨别(P=0.001)和记忆(P=0.007)方面表现出优于ICSI的表现。这两个群体之间的性别差异比较得出了性别二型性的证据。ICSI女性在习得性学习方面表现出相对于CTL女性的缺陷(P<；0.001)，但在CTL和ICSI男性之间没有显著差异。在辨别任务和记忆任务中，ICSI男性比CTL男性存在缺陷(P=0.002.0 5和P=0.0 2)，但女性在这些任务上的差异不显著。在对12个月大的小鼠进行的辨别或记忆保持/再习得评估中，没有差异。在实验过程中，ICSI男性和女性在所有时间点上的体重都明显高于CTL同行。大规模数据N/A限制，谨慎的理由研究不是盲目的。所有的学习评估都利用了食物奖励；需要对操纵性学习、巴甫洛夫学习和非联想学习进行其他评估，以充分描述ICSI小鼠的学习特征，并推测通过ICSI受孕的人类认知功能的影响。研究小鼠模型学习和记忆过程的研究结果具有更广泛的意义，有可能在认知功能水平上阐明ICSI的结果。未来的研究应该使用多种学习范式，评估男性和女性，并调查与ICSI程序相关的变量的影响。研究ICSI的认知功能是一项跨学科的努力，需要研究人员在遗传和心理分析层面上进行协调。研究资金/竞争兴趣(S)这项工作得到了美国国立卫生研究院(P30GM110767、HD071736和HD085506给W.Y.)、邓普顿基金会(61174到W.Y.)的资助。以及内华达大学雷诺研究与创新办公室颁发的新学术奋进奖(授予M.L.，Y.W.，H.Z.，L.H.和W.Y.)。作者声明不存在利益冲突。
STUDY QUESTION Are there differences in operant learning and memory between mice born through ICSI and naturally conceived control (CTL) mice? SUMMARY ANSWER ICSI females exhibited deficits in the acquisition reward learning relative to CTL females, and ICSI males exhibited deficiencies in discrimination learning and memory relative to CTL males. WHAT IS KNOWN ALREADY Some human outcome studies have suggested that ICSI might be associated with an increased risk of certain cognitive disorders, but only one of two behavioral studies with ICSI mouse models have reported differences between ICSI and CTL females. No studies to date have investigated associative learning in ICSI mice. STUDY DESIGN, SIZE, DURATION Groups of 36 ICSI mice (18 male, 18 female) and 37 CTL mice (19 male, 18 female) aged 3-6 months were compared in a series of operant learning procedures that assessed acquisition of a new behavior, discrimination learning and memory. In total, 16 ICSI mice (9 male, 7 female) and 17 CTL mice (10 male, 7 female) received follow-up discrimination learning and memory assessments at 12 months of age (6 months after the end of initial training) to evaluate retention and reacquisition of learned performances. PARTICIPANTS/MATERIALS, SETTING, METHODS Mice received daily operant learning sessions in experimental chambers in which all stimulus events and the recording of responses were automated. Food rewards were delivered for responding under different conditions of reinforcement, which varied by procedure. Subjects received a successive series of sessions of nose poke acquisition training, discrimination training and the delayed-non-matching-to-position memory procedure. Mixed repeated measures ANOVAs in which the between-subjects factor was group (ICSI vs CTL) and the within-subjects factor was repeated exposures to learning procedures (i.e. sessions) were used to analyze data. MAIN RESULTS AND THE ROLE OF CHANCE In comparisons between all mice (i.e. males and females combined), CTL mice exhibited superior performance relative to ICSI in response acquisition (P = 0.03), discrimination (P = 0.001) and memory (P = 0.007). Sex-specific comparisons between the groups yielded evidence of sexual dimorphism. ICSI females exhibited a deficit in acquisition learning relative to CTL females (P < 0.001), but there was not a significant difference between CTL and ICSI males. In the discrimination and memory tasks, ICSI males exhibited deficits relative to CTL males (P = 0.002 and P = 0.02, respectively) but the differences between females in these tasks were not significant. There was no difference in discrimination or memory retention/re-acquisition assessments conducted with mice at 12 months of age. ICSI males and females weighed significantly more than CTL counterparts at all points during the experiment. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION The study was not blinded. All learning assessments utilized food reward; other assessments of operant, Pavlovian and nonassociative learning are needed to fully characterize learning in ICSI mice and speculate regarding the implications for cognitive function in humans conceived via ICSI. WIDER IMPLICATIONS OF THE FINDINGS Studying learning and memory processes in mouse models have the potential to shed light on ICSI outcomes at the level of cognitive function. Future research should use multiple learning paradigms, assess both males and females, and investigate the effects of variables related to the ICSI procedure. Studying cognitive function in ICSI is an interdisciplinary endeavor and requires co-ordination between researchers at the genetic and psychological levels of analysis. STUDY FUNDING/COMPETING INTEREST(S) This work was supported, in part, by grants from the NIH (P30GM110767, HD071736 and HD085506 to W.Y.), the Templeton Foundation (61174 to W.Y.) and a New Scholarly Endeavor Grant from the University of Nevada, Reno Office of Research and Innovation (to M.L., Y.W., H.Z., L.H. and W.Y.). The authors declare no competing interests.