Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Statistics, School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
Biol Psychiatry. 2018 Apr 15;83(8):670-679. doi: 10.1016/j.biopsych.2017.11.029. Epub 2017 Dec 7.
Visuospatial working memory (vsWM), which is impaired in schizophrenia, requires information transfer across multiple nodes in the cerebral cortex, including visual, posterior parietal, and dorsolateral prefrontal regions. Information is conveyed across these regions via the excitatory projections of glutamatergic pyramidal neurons located in layer 3, whose activity is modulated by local inhibitory gamma-aminobutyric acidergic (GABAergic) neurons. Key properties of these neurons differ across these cortical regions. Consequently, in schizophrenia, alterations in the expression of gene products regulating these properties could disrupt vsWM function in different ways, depending on the region(s) affected.
Here, we quantified the expression of markers of glutamate and GABA neurotransmission selectively in layer 3 of four cortical regions in the vsWM network from 20 matched pairs of schizophrenia and unaffected comparison subjects.
In comparison subjects, levels of glutamate transcripts tended to increase, whereas GABA transcript levels tended to decrease, from caudal to rostral, across cortical regions of the vsWM network. Composite measures across all transcripts revealed a significant effect of region, with the glutamate measure lowest in the primary visual cortex and highest in the dorsolateral prefrontal cortex, whereas the GABA measure showed the opposite pattern. In schizophrenia subjects, the expression levels of many of these transcripts were altered. However, this disease effect differed across regions, such that the caudal-to-rostral increase in the glutamate measure was blunted and the caudal-to-rostral decline in the GABA measure was enhanced in the illness.
Differential alterations in layer 3 glutamate and GABA neurotransmission across cortical regions may contribute to vsWM deficits in schizophrenia.
精神分裂症患者的视空间工作记忆（vsWM）受损，这需要大脑皮层多个节点之间的信息传递，包括视觉、顶后和背外侧前额叶区域。信息通过位于第 3 层的谷氨酸能锥体神经元的兴奋性投射在这些区域之间传递，其活性受局部抑制性γ-氨基丁酸能（GABAergic）神经元的调节。这些神经元的关键特性在这些皮层区域之间有所不同。因此，在精神分裂症中，调节这些特性的基因产物的表达改变可能以不同的方式破坏 vsWM 功能，具体取决于受影响的区域。
在这里，我们定量分析了谷氨酸和 GABA 神经递质在 vsWM 网络的四个皮层区域的第 3 层中选择性表达的标记物，这些区域来自 20 对匹配的精神分裂症和未受影响的对照组受试者。
在对照组中，谷氨酸转录本的水平倾向于从尾到头增加，而 GABA 转录本的水平倾向于从尾到头减少，跨越 vsWM 网络的皮层区域。所有转录本的综合测量显示出区域的显著影响，谷氨酸测量值在初级视觉皮层最低，在背外侧前额叶皮层最高，而 GABA 测量值则相反。在精神分裂症患者中，许多这些转录本的表达水平发生了改变。然而，这种疾病效应在区域之间存在差异，使得谷氨酸测量值的从尾到头的增加变平，而 GABA 测量值的从尾到头的下降增强。
皮层区域间第 3 层谷氨酸和 GABA 神经递质的差异改变可能导致精神分裂症的 vsWM 缺陷。
