神经递质受体构筑将局部神经化学与语义记忆联系起来
Neurotransmitter receptor architecture links local neurochemistry to semantic memory
前颞叶是语义记忆的关键枢纽,其GABA能与谷氨酸能神经化学与语义记忆表现有关,但背后的受体分子构筑尚不清楚。研究结合影像转录组学与活体磁共振波谱,估计个体特异的受体亚基基因表达空间分布,并测量前颞叶局部GABA+与Glx浓度。结果显示GABA能受体基因与GABA+、谷氨酸能受体基因与Glx存在对应耦合,前颞叶GABA+和Glx浓度与语义记忆成绩正相关,中介分析提示GABA+与Glx分别承载不同受体构筑与语义记忆之间的关联。材料仅为摘要,尚未经同行评审。
A fundamental challenge in neuroscience is understanding how the molecular and neurochemical architecture of the human cortex gives rise to sophisticated higher cognitive functions. The anterior temporal lobe (ATL) is a key hub for semantic memory, and its underlying GABAergic and glutamatergic neurochemistry supports semantic memory performance. However, the molecular receptor architecture underlying these neurochemical-cognitive relationships remains unknown. Here, we combined imaging transcriptomics and in vivo magnetic resonance spectroscopy (MRS) to investigate how neurotransmitter receptor organisation relates to local neurochemistry and semantic memory in the human ATL. We found that the ATL exhibited a distinct transcriptomically inferred receptor-subunit profile relative to control cortical regions (occipital cortex and vertex). Individual-specific spatial estimates of receptor-subunit gene expression were systematically associated with local GABA+ and Glx concentrations, revealing preferential coupling between GABAergic receptor genes and GABA+ and between glutamatergic receptor genes and Glx, alongside widespread cross-system associations between GABAergic receptor architecture and Glx. ATL GABA+ and Glx concentrations were positively associated with semantic memory performance, and GABAergic and glutamatergic receptor-subunit expression showed selective relationships with semantic memory accuracy. Crucially, mediation analyses revealed that GABA+ mediated associations between GABAergic receptor architecture and semantic performance, whereas Glx mediated both glutamatergic and widespread GABAergic receptor associations. Together, these findings reveal a coupled molecular-neurochemical architecture of the human ATL, linking neurotransmitter receptor organisation to regional neurochemical state and individual differences in semantic memory. Our findings provide a multiscale account of how cortical molecular organisation is associated with human higher cogni
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来源:bioRxiv · Neuroscience · biorxiv.org