Interference of commissural connections through the genu of the corpus callosum specifically impairs sensorimotor gating
Interference of commissural connections through the genu of the corpus callosum specifically impairs sensorimotor gating
复制标题
通过胼胝体膝部的连合连接的干扰特别损害感觉运动门控
DOI：
10.1016/j.bbr.2021.113383
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发表时间：
2021-05-28
影响因子：
2.7
通讯作者：
Tao，Yanmei
中科院分区：
文献类型：
--
作者：
Xiao，Guanxiu;Li，Huashun;Tao，Yanmei
精神分裂症患者的白质异常具有区域性束特异性。胼胝体膝部的髓磷脂缺失是不同人群中精神分裂症患者最一致的发现之一。我们通过将顺行轴突追踪病毒载体立体定向注射到一侧半球的胼胝体小钳中，对穿过 GCC 的轴突进行了表征，并鉴定了前额叶皮层两个半球中具有连合连接的同位脑结构，包括前扣带区、前边缘区、次级运动区和无颗粒岛叶区的背侧部分，以及与初级运动区、尾壳核和屏状体的连合连接。为了研究这些连合连接中的髓鞘形成障碍是否对精神分裂症症状的发展至关重要，我们通过立体定向注射脱髓鞘剂溶血卵磷脂到海湾合作委员会局灶性脱髓鞘的小鼠模型中，并在一系列用于模拟精神分裂症样症状域的行为任务中测试了这些小鼠。我们发现海湾合作委员会的脱髓鞘既不影响社交兴趣或情绪状态，也不影响运动活动或运动协调。然而，它特别减少了声惊吓的前脉冲抑制，这是一种众所周知的感觉运动门控措施。这项研究增进了我们对 GCC 特异性白质病变对相关疾病的病理生理学贡献的理解，并证明了额叶皮质之间的半球间通讯对于感觉运动门控的自上而下调节的不可或缺的作用。
White matter abnormalities in schizophrenic patients are characterized as regional tract-specific. Myelin loss at the genu of the corpus callosum (GCC) is one of the most consistent findings in schizophrenic patients across the different populations. We characterized the axons that pass through the GCC by stereotactically injecting an anterograde axonal tracing viral vector into the forceps minor of the corpus callosum in one hemisphere, and identified the homotopic brain structures that have commissural connections in the two hemispheres of the prefrontal cortex, including the anterior cingulate area, the prelimbic area, the secondary motor area, and the dorsal part of the agranular insular area, along with commissural connections with the primary motor area, caudoputamen, and claustrum. To investigate whether dysmyelination in these commissural connections is critical for the development of schizophrenia symptoms, we generated a mouse model with focal demyelination at the GCC by stereotactically injecting demyelinating agent lysolecithin into this site, and tested these mice in a battery of behavioral tasks that are used to model the schizophrenia-like symptom domains. We found that demyelination at the GCC influenced neither the social interest or mood state, nor the locomotive activity or motor coordination. Nevertheless, it specifically reduced the prepulse inhibition of acoustic startle that is a well-known measure of sensorimotor gating. This study advances our understanding of the pathophysiological contributions of the GCC-specific white matter lesion to the related disease, and demonstrates an indispensable role of interhemispheric communication between the frontal cortices for the top-down regulation of the sensorimotor gating.