大鼠注意定势转移任务模型的深入研究：种系和检测程序的影响

Further Study on the Attentional Set-shifting Task in Rats: Effects of Strain and Testing Protocol

注意定势转移任务(attentional set-shifting task,AST)可用于特异性检测啮齿类动物前额叶皮层及其皮层下神经通路介导的认知灵活性,是目前研究认知灵活性及其障碍神经基础的重要模型。本研究系统调查了大鼠种系和检测程序差异对AST结果的影响。通过比较Wistar和Sprague Dawley(SD)两个种系大鼠在七阶段和五阶段两种AST检测程序中的认知表现,研究发现:(1)SD和Wistar大鼠前额叶认知功能存在差异,后者的总体认知表现优于前者。尤其是Wistar大鼠在逆反学习阶段的达标训练次数及错误率显著低于SD大鼠,表明Wistar大鼠具有更高的策略转换灵活性。(2)在AST测试中逆反学习和外维度定势转移是认知灵活性评价的核心指标。这两种认知转换过程分别以前期策略和注意定势建立为基础。结果显示在两种AST检测程序中Wistar和SD大鼠在逆反学习和/或外维度定势转移等复杂学习阶段的达标训练次数和错误率均高于其它简单关联学习阶段,表明在目前实验条件下大鼠均表现出定势形成和转换困难的反应模式,不同认知反应间的结构关系具有稳定性。这些结果提示大鼠前额叶皮质介导的认知灵活性存在种系差异,AST各阶段认知反应间的结构效度不受目前使用的大鼠种系和检测程序差异的影响,扩展了对AST模型的认识。

Attentional set-shifting task （AST） is a newly developed rodent-based model that can be used to specifically evaluate cortically-mediated cognitive flexibility. The AST has been increasingly used to investigate the neural basis underlying cognitive flexibility and related disorders. In the present study, we investigated the effects of strain and testing protocol on cognitive function by comparing the performance during different cognitive stages in the AST, between Sprague-Dawley （SD） and Wistar rats, and between a seven-stage and five-stage AST. Our data showed differences in cortically-mediated cognitive function between SD and Wistar rats when they were tested in both seven-stage and five-stage AST. In general, Wistar rats exhibited better performance in each stage of the AST compared with SD rats. Especially in the reversal learning （RL） stage, Wistar rats required fewer trials to reach the criterion and lower error rates compared with SD rats, suggesting better cognitive flexibility in strategy shifting. In contrast, the reactive pattern between different cognitive stages （simple discrimination, SD; compound discrimination, CD; intra-dimensional shifting, IDS; reversal learning, RL;extra-dimensional shifting, EDS） in the AST did not significantly differ by strain or testing protocol. Theoretically, there is a general response pattern across these cognitive stages, namely, more trials to reach criterion and/or higher error rates are generally seen during higher complexity learning stages （i.e. RL and EDS） than in simpler learning stages （i.e. SD and CD）, which is a prerequisite for the interpretation of performance in the RL and EDS in terms of strategy and attentional set-shifting. Consistent with this, we found that both SD and Wistar rats required more trials to reach criterion and showed higher error rates during RL and/or EDS stages than other stages in both the five-stage and seven-stage AST, demonstrating a stable reactive pattern of set establishment and set shifting in the AST. These results suggest that there are strain differences in cortically-mediated cognitive flexibility in rats, and constructive relationship across different cognitive components in the AST is stable across rat strain and testing protocol. These findings extend the extant knowledge of the AST model and provide a behavioral basis for the selection of experimental animal and testing protocols for the AST in further studies.