Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Schubertstraße 42, 01309, Dresden, Germany.
Department of Human Genetics, Ruhr-University Bochum, Bochum, Germany.
Mol Neurobiol. 2019 Sep;56(9):6134-6141. doi: 10.1007/s12035-019-1521-6. Epub 2019 Feb 7.
The cholinergic system is one of the most important neurotransmitter systems, but knowledge about the relevance of the cholinergic muscarinergic receptor system for cognitive functions is still scarce. Evidence suggests that the cholinergic muscarinic 2 receptor (CHRM2) plays an important role in the processing of cueing/prior information that help to increase the efficacy of lower-level attentional processes. In the current study, we investigated whether this is also the case for higher-level cognitive flexibility mechanisms. To this end, we tested N = 210 healthy adults with a backward inhibition task, in which prior information needs to be used to guide cognitive flexibility mechanisms. Testing different polymorphisms of the CHRM2 gene, we found that variation in this gene play a role in cognitive flexibility. It could be demonstrated that rs8191992 TT genotype carriers are better able to suppress no longer relevant information and to use prior information for cognitive flexibility, compared to A allele carriers. We further found that rs2350780 GG genotype carriers performed worse than A allele carriers. The results broaden the relevance of the CHRM2 system for cognitive functions beyond attentional selection processes. Corroborating recent theories on the relevance of the cholinergic system for cognitive processes, these results suggest that CHRM2 is important to process of "prior information" needed to inform subsequent cognitive operations. Considering the importance of prior information for adaptive behavioral control, it is possible that CHRM2 also modulates other instances of higher-level cognitive processes as long as these require the processing of "prior information."
胆碱能系统是最重要的神经递质系统之一，但关于胆碱能毒蕈碱受体系统与认知功能的相关性的知识仍然很少。有证据表明，胆碱能毒蕈碱 2 型受体（CHRM2）在处理提示/先验信息方面发挥着重要作用，这些信息有助于提高较低水平注意过程的效率。在目前的研究中，我们研究了这是否也是高级认知灵活性机制的情况。为此，我们测试了 210 名健康成年人的反向抑制任务，在该任务中需要使用先验信息来指导认知灵活性机制。测试 CHRM2 基因的不同多态性，我们发现该基因的变异在认知灵活性中起作用。可以证明，与 A 等位基因携带者相比，rs8191992 TT 基因型携带者能够更好地抑制不再相关的信息，并利用先验信息进行认知灵活性。我们进一步发现，rs2350780 GG 基因型携带者的表现不如 A 等位基因携带者。研究结果拓宽了 CHRM2 系统对认知功能的相关性，超越了注意力选择过程。这些结果与最近关于胆碱能系统对认知过程相关性的理论相吻合，表明 CHRM2 对于“先验信息”的处理很重要，这些信息是告知后续认知操作所必需的。考虑到先验信息对适应性行为控制的重要性，只要这些需要处理“先验信息”，CHRM2 就有可能调节其他高级认知过程的实例。
