Thompson Shannon M, Josey Megan, Holmes Andrew, Brigman Jonathan L
Department of Neurosciences, University of New Mexico School of Medicine.
Laboratory of Behavioral and Genomic Neuroscience, National Institutes of Health.
Behav Neurosci. 2015 Apr;129(2):105-12. doi: 10.1037/bne0000045.
The ability to attend to appropriate stimuli, to plan actions and then alter those actions when environmental conditions change, is essential for an organism to thrive. There is increasing evidence that these executive control processes are mediated in part by N-methyl-D-aspartate receptors (NMDAR). NMDAR subunits confer different physiological properties to the receptor, interact with distinct intracellular postsynaptic scaffolding and signaling molecules and are differentially expressed during development. Recent findings have suggested that the GluN2B subunit may play a unique role in both the acquisition of adaptive choice and the behavioral flexibility required to shift between choices. Here we investigated the role of GluN2B containing NMDARs in the ability to learn, reverse and shift between stimulus dimensions. Mutant mice (floxed-GluN2B x CaMKII-Cre) lacking GluN2B in the dorsal CA1 of the hippocampus and throughout the cortex were tested on an attentional set-shifting task. To explore the role that alterations in motor behavior may have on these behaviors, gross and fine motor behaviors were analyzed in mutant and floxed-control mice. Results show that corticohippocampal loss of GluN2B selectively impaired an initial reversal in a stimulus specific manner and impaired the ability of mutant mice to form an attentional set. Further, GluN2B mice showed normal motor behavior in both overall movement and individual limb behaviors. Together, these results further support the role of NMDAR, and GluN2B in particular, in aspects of executive control including behavioral flexibility and attentional processes.
能够关注适当的刺激，规划行动，并在环境条件变化时改变这些行动，对于生物体的茁壮成长至关重要。越来越多的证据表明，这些执行控制过程部分由N-甲基-D-天冬氨酸受体（NMDAR）介导。NMDAR亚基赋予受体不同的生理特性，与不同的细胞内突触后支架和信号分子相互作用，并在发育过程中差异表达。最近的研究结果表明，GluN2B亚基可能在适应性选择的获得以及在不同选择之间转换所需的行为灵活性方面发挥独特作用。在这里，我们研究了含有GluN2B的NMDAR在学习、反转以及在刺激维度之间转换能力中的作用。在注意力转换任务中测试了海马背侧CA1区和整个皮质中缺乏GluN2B的突变小鼠（floxed-GluN2B x CaMKII-Cre）。为了探究运动行为改变可能对这些行为产生的作用，对突变小鼠和floxed对照小鼠的粗略和精细运动行为进行了分析。结果表明，皮质海马区GluN2B的缺失以刺激特异性方式选择性损害了初始反转，并损害了突变小鼠形成注意力集的能力。此外，GluN2B小鼠在整体运动和单个肢体行为方面均表现出正常的运动行为。总之，这些结果进一步支持了NMDAR，尤其是GluN2B在包括行为灵活性和注意力过程在内的执行控制方面的作用。
