Brigman Jonathan L, Daut Rachel A, Saksida Lisa, Bussey Timothy J, Nakazawa Kazu, Holmes Andrew
aDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico bLaboratory of Behavioral and Genomic Neuroscience, NIAAA, NIH Rockville, Maryland cDepartment of Psychiatry, University of Alabama School of Medicine, Birmingham, Alabama, USA dDepartment of Experimental Psychology, Medical Research Council and Wellcome Trust Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
Neuroreport. 2015 Jun 17;26(9):489-94. doi: 10.1097/WNR.0000000000000373.
Previous studies have established a role for N-methyl-D-aspartate receptor (NMDAR) containing the GluN2B subunit in efficient learning behavior on a variety of tasks. Recent findings have suggested that NMDAR on GABAergic interneurons may underlie the modulation of striatal function necessary to balance efficient action with cortical excitatory input. Here we investigated how loss of GluN2B-containing NMDAR on GABAergic interneurons altered corticostriatal-mediated associative learning. Mutant mice (floxed-GluN2B×Ppp1r2-Cre) were generated to produce loss of GluN2B on forebrain interneurons and phenotyped on a touchscreen-based pairwise visual learning paradigm. We found that the mutants showed normal performance during Pavlovian and instrumental pretraining, but were significantly impaired on a discrimination learning task. Detailed analysis of the microstructure of discrimination performance revealed reduced win→stay behavior in the mutants. These results further support the role of NMDAR, and GluN2B in particular, on modulation of striatal function necessary for efficient choice behavior and suggest that NMDAR on interneurons may play a critical role in associative learning.
先前的研究已经确定，含有GluN2B亚基的N-甲基-D-天冬氨酸受体（NMDAR）在多种任务的有效学习行为中发挥作用。最近的研究结果表明，GABA能中间神经元上的NMDAR可能是调节纹状体功能的基础，而纹状体功能对于平衡有效行为与皮质兴奋性输入是必要的。在此，我们研究了GABA能中间神经元上含GluN2B的NMDAR缺失如何改变皮质纹状体介导的联想学习。生成了突变小鼠（floxed-GluN2B×Ppp1r2-Cre），以使前脑中间神经元上的GluN2B缺失，并在基于触摸屏的配对视觉学习范式上对其进行表型分析。我们发现，突变小鼠在巴甫洛夫式和工具性预训练期间表现正常，但在辨别学习任务上显著受损。对辨别性能微观结构进行的详细分析显示，突变小鼠中“赢→保持”行为减少。这些结果进一步支持了NMDAR，尤其是GluN2B在调节有效选择行为所需的纹状体功能中的作用，并表明中间神经元上的NMDAR可能在联想学习中起关键作用。
