Institute of Neuroscience, Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
Institute of Neuroscience, Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Soft Matter Research Center, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Neuroscience. 2014 Mar 7;261:107-17. doi: 10.1016/j.neuroscience.2013.12.040. Epub 2013 Dec 27.
Both neuregulin 1 (NRG1) and its receptor ErbB4 are susceptibility genes for schizophrenia. Reduced synchronization of evoked oscillations in several cortical regions, especially in the prefrontal cortex, is associated with the core symptoms of schizophrenia. Recent studies have reported that NRG1 may affect the hippocampal oscillations. However, the role of NRG1/ErbB4 signaling in the synchronization of neurons in the prefrontal cortex is unclear. Here, we found that NRG1 enhanced the synchrony of pyramidal neurons via presynaptic interneurons. Meanwhile, NRG1 also increased the synchrony between pairs of fast-spiking interneurons and pairs of fast-spiking and non-fast-spiking interneurons in the prefrontal cortex, and this effect was mediated by ErbB4 receptors. Moreover, the NRG1-enhanced synchrony of interneurons was through their mutually-inhibitory synapses but not electrical coupling. Furthermore, kainate-induced gamma oscillations in vivo were enhanced by NRG1 and did not change in Dlx5/6-ErbB4(-/-) mice in which the ErbB4 receptors were specifically knocked out in interneurons of the frontal brain. Overall, our findings suggested that NRG1/ErbB4 signaling plays an important role in the synchronized oscillations of the whole network in the prefrontal cortex that are impaired in schizophrenia.
神经调节蛋白 1（NRG1）及其受体 ErbB4 均为精神分裂症的易感基因。几个皮质区域（尤其是前额皮质）的诱发电位振荡同步性降低与精神分裂症的核心症状有关。最近的研究报道称，NRG1 可能会影响海马体的振荡。然而，NRG1/ErbB4 信号在前额皮质神经元同步中的作用尚不清楚。在这里，我们发现 NRG1 通过突触前中间神经元增强了锥体神经元的同步性。同时，NRG1 还增加了前额皮质中快速放电中间神经元与快速放电和非快速放电中间神经元对之间的同步性，并且这种作用是由 ErbB4 受体介导的。此外，NRG1 增强中间神经元的同步性是通过它们的相互抑制性突触而不是电耦合。此外，NRG1 增强了体内的海人酸诱导的γ 振荡，而在 Dlx5/6-ErbB4（-/-）小鼠中则没有改变，其中 ErbB4 受体在前脑中间神经元中特异性敲除。总体而言，我们的研究结果表明，NRG1/ErbB4 信号在精神分裂症中受损的前额皮质整个网络的同步振荡中发挥重要作用。
