BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS Differential alterations in layer 3 glutamate and GABA neurotransmission across cortical regions may contribute to vsWM deficits in schizophrenia.

中文翻译：

---

精神分裂症皮质视觉空间工作记忆网络中谷氨酸和 GABA 转录本的梯度变化

背景视觉空间工作记忆 (vsWM) 在精神分裂症中受损，需要跨大脑皮层的多个节点传递信息，包括视觉、后顶叶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，其活动受局部抑制性 γ-氨基丁酸 (GABAergic) 神经元调节。这些神经元的关键特性在这些皮质区域中有所不同。因此，在精神分裂症中，调节这些特性的基因产物表达的改变可能会以不同的方式破坏 vsWM 功能，具体取决于受影响的区域。方法在这里，我们从 20 对匹配的精神分裂症和未受影响的比较对象中，选择性地量化了 vsWM 网络中四个皮质区域的第 3 层中谷氨酸和 GABA 神经传递标志物的表达。结果 在比较对象中，谷氨酸转录物水平趋于增加，而 GABA 转录物水平趋于降低，从尾部到嘴侧，跨越 vsWM 网络的皮质区域。所有转录本的综合测量显示区域的显着影响，谷氨酸测量在初级视觉皮层最低，在背外侧前额叶皮层最高，而 GABA 测量显示出相反的模式。在精神分裂症受试者中，许多这些转录物的表达水平发生了改变。然而，这种疾病的影响因地区而异，因此，在疾病中，谷氨酸盐量从尾端到头端的增加减弱，而 GABA 量从尾端到头端的下降加剧。结论 跨皮质区域的第 3 层谷氨酸和 GABA 神经传递的差异改变可能导致精神分裂症的 vsWM 缺陷。