A dopaminergic gene cluster in the prefrontal cortex predicts performance indicative of general intelligence in genetically heterogeneous mice.
A dopaminergic gene cluster in the prefrontal cortex predicts performance indicative of general intelligence in genetically heterogeneous mice.
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DOI：
10.1371/journal.pone.0014036
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发表时间：
2010-11-17
期刊：
影响因子：
3.7
通讯作者：
Matzel LD
中科院分区：
文献类型：
--
作者：
Kolata S;Light K;Wass CD;Colas-Zelin D;Roy D;Matzel LD
遗传异质性小鼠表现出一种在质量和心理测量学上类似于人类一般智力的特征，并且与人类一样，这种特征与工作记忆的处理效能（包括其对选择性注意力的依赖）共同变化。研究表明，前额叶皮质（PFC）中的多巴胺信号对动物在工作记忆和选择性注意任务中的表现发挥着关键作用。由于PFC在调节工作记忆中的这种作用，在这里我们比较了60只遗传多样的CD-1小鼠的PFC基因表达谱，这些小鼠表现出广泛的一般学习能力（即，在五个不同的学习任务中的综合表现）。动物的一般认知能力首先基于它们在一组五个不同学习任务中的总体表现来确定。通过设计一个程序来最大限度地减少假阳性识别，基因表达微阵列（由125，000个基因组成）的分析确定了少数（<20个）在表现出快速和缓慢聚集学习能力的动物中差异表达的基因。在这些基因中，鉴定出一个功能簇，该簇（Darpp-32，Drd 1a和Rgs 9）是多巴胺信号传导的既定调节剂。随后的定量PCR发现，这些多巴胺能基因和一个血管基因（Nudt 6）的表达与个体动物的一般认知表现显着相关。这些结果表明，D1介导的多巴胺信号在PFC，可能通过其调制的工作记忆，是预测的一般认知能力。此外，这些结果提供了可能潜在地调节一般智力的特定分子途径的第一个直接证据。
Genetically heterogeneous mice express a trait that is qualitatively and psychometrically analogous to general intelligence in humans, and as in humans, this trait co-varies with the processing efficacy of working memory (including its dependence on selective attention). Dopamine signaling in the prefrontal cortex (PFC) has been established to play a critical role in animals' performance in both working memory and selective attention tasks. Owing to this role of the PFC in the regulation of working memory, here we compared PFC gene expression profiles of 60 genetically diverse CD-1 mice that exhibited a wide range of general learning abilities (i.e., aggregate performance across five diverse learning tasks). Animals' general cognitive abilities were first determined based on their aggregate performance across a battery of five diverse learning tasks. With a procedure designed to minimize false positive identifications, analysis of gene expression microarrays (comprised of ≈25,000 genes) identified a small number (<20) of genes that were differentially expressed across animals that exhibited fast and slow aggregate learning abilities. Of these genes, one functional cluster was identified, and this cluster (Darpp-32, Drd1a, and Rgs9) is an established modulator of dopamine signaling. Subsequent quantitative PCR found that expression of these dopaminegic genes plus one vascular gene (Nudt6) were significantly correlated with individual animal's general cognitive performance. These results indicate that D1-mediated dopamine signaling in the PFC, possibly through its modulation of working memory, is predictive of general cognitive abilities. Furthermore, these results provide the first direct evidence of specific molecular pathways that might potentially regulate general intelligence.
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DOI：
10.1016/j.cub.2010.02.034
发表时间：
2010-04-27
期刊：
Current biology : CB
影响因子：
--
作者：
Light KR;Kolata S;Wass C;Denman-Brice A;Zagalsky R;Matzel LD
通讯作者：
Matzel LD
影响因子：
3.4
作者：
Garzón, J;Rodríguez-Díaz, M;Sánchez-Blázquez, P
通讯作者：
Sánchez-Blázquez, P
影响因子：
2.9
作者：
GomezPinilla, F;Dao, L;So, V
通讯作者：
So, V
DOI：
10.1016/j.bbamcr.2004.01.005
发表时间：
2004-05-03
影响因子：
5.1
作者：
Bouhamdan, M;Michelhaugh, SK;Bannon, MJ
通讯作者：
Bannon, MJ
影响因子：
1.9
作者：
Grossman, Henya C.;Hale, Gregory;Matzel, Louis D.
通讯作者：
Matzel, Louis D.