Li Jin, Liu Bing, Chen Chuansheng, Cui Yue, Shang Liqing, Zhang Yun, Wang Chao, Zhang Xiaolong, He Qinghua, Zhang Wen, Bi Wenwei, Jiang Tianzi
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.
National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.
Hum Brain Mapp. 2015 Nov;36(11):4372-82. doi: 10.1002/hbm.22924. Epub 2015 Aug 7.
Calbindin-containing γ-aminobutyric acid (GABA)ergic interneurons in the prefrontal cortex (PFC) have been found to play an important role in working memory (WM) and their malfunctions have been linked to psychiatric disorders. A recent genome-wide association and expression-SNP study indicated that the RAB2A gene was associated with the density of prefrontal calbindin-positive neurons, suggesting this gene may have a broader influence on prefrontal structure and function. Using multimodal MRI and behavioral tasks, the current study investigated the effect of RAB2A on prefrontal morphology, resting-state functional connectivity, and WM performance in a large sample of healthy Han Chinese subjects. Results showed that the RAB2A AGCAAA haplotype was associated with improved WM accuracy, increased cortical thickness in the left inferior frontal gyrus, and decreased functional connectivity between the left inferior frontal gyrus and the left dorsolateral PFC. Our findings provide consistent evidence supporting the effect of RAB2A on the structure and function of the PFC and related cognitive functions. These results should provide new insights into the neural mechanisms underlying the GABAergic genes' role in WM as well as its dysfunction.
前额叶皮质（PFC）中含钙结合蛋白的γ-氨基丁酸（GABA）能中间神经元已被发现对工作记忆（WM）起着重要作用，其功能障碍与精神疾病有关。最近一项全基因组关联和表达单核苷酸多态性研究表明，RAB2A基因与前额叶钙结合蛋白阳性神经元的密度有关，这表明该基因可能对前额叶的结构和功能有更广泛的影响。本研究使用多模态磁共振成像（MRI）和行为任务，在一大群健康汉族受试者中调查了RAB2A对前额叶形态、静息态功能连接和工作记忆表现的影响。结果显示，RAB2A AGCAAA单倍型与工作记忆准确性提高、左侧额下回皮质厚度增加以及左侧额下回与左侧背外侧前额叶皮质之间的功能连接减少有关。我们的研究结果提供了一致的证据，支持RAB2A对前额叶皮质结构和功能以及相关认知功能的影响。这些结果应为GABA能基因在工作记忆中的作用及其功能障碍的神经机制提供新的见解。
