Shin Yim Yeong, Park Ashley, Berrios Janet, Lafourcade Mathieu, Pascual Leila M, Soares Natalie, Yeon Kim Joo, Kim Sangdoo, Kim Hyunju, Waisman Ari, Littman Dan R, Wickersham Ian R, Harnett Mark T, Huh Jun R, Choi Gloria B
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nature. 2017 Sep 28;549(7673):482-487. doi: 10.1038/nature23909. Epub 2017 Sep 13.
Viral infection during pregnancy is correlated with increased frequency of neurodevelopmental disorders, and this is studied in mice prenatally subjected to maternal immune activation (MIA). We previously showed that maternal T helper 17 cells promote the development of cortical and behavioural abnormalities in MIA-affected offspring. Here we show that cortical abnormalities are preferentially localized to a region encompassing the dysgranular zone of the primary somatosensory cortex (S1DZ). Moreover, activation of pyramidal neurons in this cortical region was sufficient to induce MIA-associated behavioural phenotypes in wild-type animals, whereas reduction in neural activity rescued the behavioural abnormalities in MIA-affected offspring. Sociability and repetitive behavioural phenotypes could be selectively modulated according to the efferent targets of S1DZ. Our work identifies a cortical region primarily, if not exclusively, centred on the S1DZ as the major node of a neural network that mediates behavioural abnormalities observed in offspring exposed to maternal inflammation.
孕期病毒感染与神经发育障碍的发生率增加相关,这在产前经历母体免疫激活(MIA)的小鼠中得到研究。我们之前表明,母体辅助性T细胞17促进受MIA影响的后代出现皮质和行为异常。在此我们表明,皮质异常优先定位于包含初级体感皮层颗粒紊乱区(S1DZ)的区域。此外,该皮质区域锥体细胞的激活足以在野生型动物中诱导出与MIA相关的行为表型,而神经活动的降低挽救了受MIA影响的后代的行为异常。社交能力和重复行为表型可根据S1DZ的传出靶点进行选择性调节。我们的研究确定了一个主要(如果不是唯一)以S1DZ为中心的皮质区域,作为神经网络的主要节点,该网络介导在暴露于母体炎症的后代中观察到的行为异常。