Epistasis between dopamine regulating genes identifies a nonlinear response of the human hippocampus during memory tasks
Epistasis between dopamine regulating genes identifies a nonlinear response of the human hippocampus during memory tasks
复制标题
DOI：
10.1016/j.biopsych.2008.02.001
复制
发表时间：
2008-08-01
影响因子：
10.6
通讯作者：
Dallapiccola, Bruno
中科院分区：
文献类型：
--
作者：
Bertolino, Alessandro;Di Giorgio, Annabella;Dallapiccola, Bruno
背景：多巴胺对前额叶皮层神经元活动的调节呈倒U型曲线。多巴胺也是调节海马介导的记忆加工的重要因素。在这里，我们研究了在不同的记忆条件下，通过儿茶酚-O-甲基转移酶（COMT）和多巴胺转运蛋白（DAT）的多巴胺失活的遗传变异对健康人海马活动的影响。方法：使用血氧水平依赖性（BOLD）功能磁共振成像（fMRI）对82名受试者进行了一系列人口统计学和遗传学变量的匹配，我们研究了COMT缬氨酸（瓦尔）（158）蛋氨酸（Met）和DAT 3'可变数目串联重复序列（VNTR）多态性对海马再认记忆编码和工作记忆功能的影响。我们的研究结果一致地证明了一种双重解离，使得DAT 9重复载体等位基因以与DAT 10/10完全相反的方向调节海马中的活性。在不同记忆条件下基于COMT瓦尔（158）Met基因型的重复等位基因。类似的结果是显而易见的腹外侧和背外侧前额叶cortex.Conclusions：这些研究结果表明，遗传决定的多巴胺信号在记忆处理映射到一个非线性的关系，也在海马。我们的数据还表明，在人类大脑中，在不同的记忆条件下，与多巴胺信号传导有关的两个基因具有上位性。
Background: Dopamine modulation of neuronal activity in prefrontal cortex maps to an inverted U-curve. Dopamine is also an important factor in regulation of hippocampal mediated memory processing. Here, we investigated the effect of genetic variation of dopamine inactivation via catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) on hippocampal activity in healthy humans during different memory conditions.Methods: Using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in 82 subjects matched for a series of demographic and genetic variables, we studied the effect of the COMT valine (Val)(158)methionine (Met) and the DAT 3' variable number tandem repeat (VNTR) polymorphisms on function of the hippocampus during encoding of recognition memory and during working memory.Results: Our results consistently demonstrated a double dissociation so that DAT 9-repeat carrier alleles modulated activity in the hippocampus in the exact opposite direction of DAT 10/10-repeat alleles based on COMT Val(158)Met genotype during different memory conditions. Similar results were evident in ventrolateral and dorsolateral prefrontal cortex.Conclusions: These findings suggest that genetically determined dopamine signaling during memory processing maps to a nonlinear relationship also in the hippocampus. Our data also demonstrate in human brain epistasis of two genes implicated in dopamine signaling on brain activity during different memory conditions.