Gorka Adam X, Knodt Annchen R, Hariri Ahmad R
Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Institute for Genome Sciences & Policy, Duke University, Durham, 27708 NC, USA
Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Institute for Genome Sciences & Policy, Duke University, Durham, 27708 NC, USA.
Soc Cogn Affect Neurosci. 2015 Apr;10(4):501-7. doi: 10.1093/scan/nsu080. Epub 2014 May 19.
Animal studies reveal that the amygdala promotes attention and emotional memory, in part, by driving activity in downstream target regions including the prefrontal cortex (PFC) and hippocampus. Prior work has demonstrated that the amygdala influences these regions directly through monosynaptic glutamatergic signaling, and indirectly by driving activity of the cholinergic basal forebrain and subsequent downstream acetylcholine release. Yet to date, no work has addressed the functional relevance of the cholinergic basal forebrain in facilitating signaling from the amygdala in humans. We set out to determine how blood oxygen level-dependent signal within the amygdala and cholinergic basal forebrain interact to predict neural responses within downstream targets. Here, we use functional connectivity analyses to demonstrate that the cholinergic basal forebrain moderates increased amygdala connectivity with both the PFC and the hippocampus during the processing of biologically salient stimuli in humans. We further demonstrate that functional variation within the choline transporter gene predicts the magnitude of this modulatory effect. Collectively, our results provide novel evidence for the importance of cholinergic signaling in modulating neural pathways supporting arousal, attention and memory in humans. Further, our results may shed light on prior association studies linking functional variation within the choline transporter gene and diagnoses of major depression and attention-deficit hyperactivity disorder.
动物研究表明，杏仁核部分通过驱动包括前额叶皮层（PFC）和海马体在内的下游目标区域的活动来促进注意力和情绪记忆。先前的研究已经证明，杏仁核通过单突触谷氨酸能信号直接影响这些区域，并通过驱动胆碱能基底前脑的活动以及随后的下游乙酰胆碱释放间接影响这些区域。然而，迄今为止，尚无研究探讨胆碱能基底前脑在促进人类杏仁核信号传导中的功能相关性。我们着手确定杏仁核和胆碱能基底前脑内的血氧水平依赖性信号如何相互作用，以预测下游目标区域内的神经反应。在此，我们使用功能连接分析来证明，在人类处理具有生物学显著性的刺激过程中，胆碱能基底前脑会调节杏仁核与PFC和海马体之间增强的连接性。我们进一步证明，胆碱转运蛋白基因内的功能变异可预测这种调节作用的大小。总体而言，我们的结果为胆碱能信号在调节支持人类觉醒、注意力和记忆的神经通路中的重要性提供了新证据。此外，我们的结果可能有助于解释先前将胆碱转运蛋白基因内的功能变异与重度抑郁症和注意力缺陷多动障碍的诊断联系起来的关联研究。
