Department of Psychology, University of Bonn, Germany.
Neuroimage. 2013 Jan 1;64:167-72. doi: 10.1016/j.neuroimage.2012.08.059. Epub 2012 Aug 28.
Dopaminergic activity is modulated by acetylcholine with relevance for cognitive functioning, as shown by pharmacological work in a rodent model. In humans, the two transmitter systems' joint effort on cognition has been described on the molecular genetic level: DRD2 rs6277, a single nucleotide polymorphism (SNP) on the dopamine D2 receptor gene and CHRNA4 rs1044396, a SNP on the nicotinic acetylcholine receptor gene interact on visuo-spatial and phonological working memory. The present study uses structural MRI and voxel based morphometry to extend this behavioral work to an intermediate phenotype on the neural level. We found significantly reduced gray matter volume in the right putamen in carriers of the DRD2 C/C and CHRNA4 T/T groups. This genotype combination has previously proven to be beneficial for working memory capacity. Results are in line with the idea that the two genes jointly influence the gating signals from subcortical structures to the prefrontal cortex.
多巴胺能活动受到乙酰胆碱的调节，这与认知功能有关，这一现象已在啮齿动物模型的药理学研究中得到证实。在人类中，这两种递质系统在认知方面的共同作用在分子遗传水平上已经得到描述：多巴胺 D2 受体基因上的 DRD2 rs6277 单核苷酸多态性（SNP）和烟碱型乙酰胆碱受体基因上的 CHRNA4 rs1044396 SNP 相互作用于视空间和语音工作记忆。本研究使用结构 MRI 和基于体素的形态计量学将这一行为学研究扩展到神经水平的中间表型。我们发现，DRD2 C/C 和 CHRNA4 T/T 基因型携带者的右侧壳核的灰质体积明显减少。这种基因型组合以前被证明对工作记忆容量有益。结果与这两个基因共同影响从皮质下结构到前额叶皮层的门控信号的观点一致。
