Mohapatra Alok Nath, Jabarin Renad, Ray Natali, Netser Shai, Wagner Shlomo
Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel.
Mol Psychiatry. 2025 Apr;30(4):1440-1452. doi: 10.1038/s41380-024-02754-8. Epub 2024 Sep 17.
Individuals diagnosed with autism spectrum disorder (ASD) show difficulty in recognizing emotions in others, a process termed emotion recognition. While human fMRI studies linked multiple brain areas to emotion recognition, the specific mechanisms underlying impaired emotion recognition in ASD are not clear. Here, we employed an emotional state preference (ESP) task to show that Cntnap2-knockout (KO) mice, an established ASD model, do not distinguish between conspecifics according to their emotional state. We assessed brain-wide local-field potential (LFP) signals during various social behavior tasks and found that Cntnap2-KO mice exhibited higher LFP theta and gamma rhythmicity than did C57BL/6J mice, even at rest. Specifically, Cntnap2-KO mice showed increased theta coherence, especially between the prelimbic cortex (PrL) and the hypothalamic paraventricular nucleus, during social behavior. Moreover, we observed significantly increased Granger causality of theta rhythmicity between these two brain areas, across several types of social behavior tasks. Finally, optogenetic stimulation of PrL pyramidal neurons in C57BL/6J mice impaired their social discrimination abilities, including in ESP. Together, these results suggest that increased rhythmicity of PrL pyramidal neuronal activity and its hyper-synchronization with specific brain regions are involved in the impaired emotion recognition exhibited by Cntnap2-KO mice.
被诊断患有自闭症谱系障碍（ASD）的个体在识别他人情绪方面存在困难，这一过程被称为情绪识别。虽然人类功能磁共振成像（fMRI）研究将多个脑区与情绪识别联系起来，但ASD中情绪识别受损的具体机制尚不清楚。在这里，我们采用了一种情绪状态偏好（ESP）任务来表明，Cntnap2基因敲除（KO）小鼠作为一种已确立的ASD模型，不会根据同种个体的情绪状态来区分它们。我们在各种社交行为任务中评估了全脑局部场电位（LFP）信号，发现Cntnap2-KO小鼠即使在休息时也比C57BL/6J小鼠表现出更高的LFPθ和γ节律性。具体而言，Cntnap2-KO小鼠在社交行为期间表现出θ相干性增加，特别是在前边缘皮层（PrL）和下丘脑室旁核之间。此外，在几种类型的社交行为任务中，我们观察到这两个脑区之间θ节律性的格兰杰因果关系显著增加。最后，对C57BL/6J小鼠的PrL锥体神经元进行光遗传学刺激会损害它们的社交辨别能力，包括在ESP任务中。总之，这些结果表明，PrL锥体神经元活动节律性增加及其与特定脑区的过度同步参与了Cntnap2-KO小鼠表现出的情绪识别受损。
