The prefrontal cortex (PFC) has been extensively studied in autism spectrum disorder (ASD) in an attempt to understand the deficits in executive and other higher brain functions related to sociability and emotion. Disruption of the excitatory/inhibitory (E/I) balance of cortical circuits is thought to underlie the pathophysiology of ASD. Recently, we showed that 15q dup mice (a model for ASD with human chromosome 15q11-13 paternal duplication) exhibit disruption of the E/I balance in layer 2/3 pyramidal neurons of the somatosensory cortex due to a decrease in the number of inhibitory synapses. However, whether there is a pathological abnormality in E/I balance in the PFC of 15q dup mice remains unknown. In this study, we found that 15q dup facilitates the activity-induced LTP of glutamate synapses onto layer 5 pyramidal neurons by shifting the E/I balance to an excitatory state, which this was associated with differences in synaptic glutamatergic and GABAergic inputs onto GABAergic fast-spiking interneurons (FSINs). Furthermore, we found that FSIN excitability was well-modulated and regulated by the constitutive activation of 5-HT2 receptors in PFC microcircuits. These results provide new insights into the cellular mechanisms underlying maintenance of optimal E/I balance in the PFC.

中文翻译：

---

在15q11-13复制自闭症小鼠模型中，血清素能调制的变化导致前额叶皮层神经元回路的突触失衡。

前额叶皮层（PFC）已在自闭症谱系障碍（ASD）中进行了广泛的研究，试图了解执行力和其他与社交和情感有关的高级大脑功能的缺陷。皮层回路的兴奋性/抑制性（E / I）平衡的破坏被认为是ASD病理生理的基础。最近，我们发现15q dup小鼠（具有人类染色体15q11-13父本复制的ASD模型）由于抑制物数量的减少，在体感皮质的第2/3层锥体神经元中表现出E / I平衡的破坏。突触。但是，尚不清楚15q dup小鼠的PFC中E / I平衡是否存在病理异常。在这项研究中，我们发现15q dup通过将E / I平衡转移到兴奋状态而促进了由活性诱导的谷氨酸突触LTP到达第5层锥体神经元的状态，这与突触型谷氨酸能和GABA能输入到GABA能快速突触中子（ FSIN）。此外，我们发现FSIN的兴奋性受到PFC微电路中5-HT2受体组成性激活的良好调节和调节。这些结果为维持PFC中最佳E / I平衡的细胞机制提供了新见解。我们发现FSIN的兴奋性受到PFC微电路中5-HT2受体组成性激活的良好调节和调节。这些结果提供了对维持PFC中最佳E / I平衡的细胞机制的新见解。我们发现FSIN的兴奋性受到PFC微电路中5-HT2受体组成性激活的良好调节和调节。这些结果提供了对维持PFC中最佳E / I平衡的细胞机制的新见解。