Imbalance of laminar-specific excitatory and inhibitory circuits of the orbitofrontal cortex in autism.
Imbalance of laminar-specific excitatory and inhibitory circuits of the orbitofrontal cortex in autism.
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DOI：
10.1186/s13229-020-00390-x
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发表时间：
2020-10-20
期刊：
影响因子：
6.2
通讯作者：
Zikopoulos B
中科院分区：
文献类型：
--
作者：
Liu X;Bautista J;Liu E;Zikopoulos B
人类眶额皮层（OFC）参与评估事件和刺激的情感意义，基于情感的学习，注意力资源的分配和社会认知。关于人类OFC中这些不同功能的结构，连接和兴奋/抑制回路相互作用，以及自闭症谱系障碍（ASD）个体中回路如何被破坏，人们知之甚少。我们使用了来自神经典型成年人和ASD患者的死后脑组织。我们研究了有髓轴突的形态和分布，在皮层层的OFC，在单轴突水平，作为兴奋性通路的代理。在相同的区域，我们还研究了所有神经元和神经化学和功能不同的抑制性神经元，表达钙结合蛋白小清蛋白（PV），钙结合蛋白（CB），钙视网膜蛋白（CR）的层状分布。我们发现，有髓轴突的密度增加一致朝向层6，而平均轴突直径并没有改变显着跨层在两组。然而，ASD组中有髓轴突的密度和直径均显著低于对照组。三种主要类型的抑制性神经元的分布模式和密度在组间是可比的，但是在ASD中跨OFC层的兴奋性神经元的密度显著降低。这项研究是有限的人类死后组织的高分辨率显微镜和免疫标记的最佳处理的可用性，特别是从个人与ASD。眶额皮层兴奋和抑制之间的平衡是其功能的核心，它评估并整合了情绪和社会线索与内部状态和外部输入。我们的初步研究结果提供了证据，椎板特定的变化与ASD的成人OFC的兴奋/抑制的比例，与整体减弱和可能的混乱的兴奋信号和相对加强的局部抑制。这些变化可能是ASD患者与边缘系统或其他皮质和杏仁核的主要OFC通信的病理基础，并可能为自闭症患者的社会互动和情绪信号传输中断提供解剖学基础。
The human orbitofrontal cortex (OFC) is involved in assessing the emotional significance of events and stimuli, emotion-based learning, allocation of attentional resources, and social cognition. Little is known about the structure, connectivity and excitatory/inhibitory circuit interactions underlying these diverse functions in human OFC, as well as how the circuit is disrupted in individuals with autism spectrum disorder (ASD). We used post-mortem brain tissue from neurotypical adults and individuals with ASD. We examined the morphology and distribution of myelinated axons across cortical layers in OFC, at the single axon level, as a proxy of excitatory pathways. In the same regions, we also examined the laminar distribution of all neurons and neurochemically- and functionally-distinct inhibitory neurons that express the calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR). We found that the density of myelinated axons increased consistently towards layer 6, while the average axon diameter did not change significantly across layers in both groups. However, both the density and diameter of myelinated axons were significantly lower in the ASD group compared with the Control group. The distribution pattern and density of the three major types of inhibitory neurons was comparable between groups, but there was a significant reduction in the density of excitatory neurons across OFC layers in ASD. This study is limited by the availability of human post-mortem tissue optimally processed for high-resolution microscopy and immunolabeling, especially from individuals with ASD. The balance between excitation and inhibition in OFC is at the core of its function, assessing and integrating emotional and social cues with internal states and external inputs. Our preliminary results provide evidence for laminar-specific changes in the ratio of excitation/inhibition in OFC of adults with ASD, with an overall weakening and likely disorganization of excitatory signals and a relative strengthening of local inhibition. These changes likely underlie pathology of major OFC communications with limbic or other cortices and the amygdala in individuals with ASD, and may provide the anatomic basis for disrupted transmission of signals for social interactions and emotions in autism.
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DOI：
10.1073/pnas.1806165115
发表时间：
2018-11-20
影响因子：
11.1
作者：
Barat, Elodie;Wirth, Sylvia;Duhamel, Jean-Rene
通讯作者：
Duhamel, Jean-Rene
影响因子：
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作者：
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影响因子：
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影响因子：
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DOI：
10.1073/pnas.1302982110
发表时间：
2013-07-16
影响因子：
11.1
作者：
Abrams, Daniel A.;Lynch, Charles J.;Menon, Vinod
通讯作者：
Menon, Vinod