Cortical disinhibition is a common feature of several mental diseases, such as schizophrenia, autism and intellectual disabilities. However, the underlying biological mechanisms are not clear. On January 12, 2021, the research group from ECNU Key Laboratory of Brain Functional Genomics, reveals the neural mechanism of cortical disinhibition implicated in schizophrenia. The paper was published in Nature Communications, with the title of Overexpression of neuregulin 1 in GABAergic interneurons results in reversible cortical. Wang Yaoyi , Zhao Bing and Wu Mengmeng , three Ph. D. candidates from School of Life Sciences in ECNU, are the co-first authors, and professor Yin Dongmin is the corresponding author.
The abstract of the paper is as follows：
Cortical disinhibition is a common feature of several neuropsychiatric diseases such as schizophrenia, autism and intellectual disabilities. However, the underlying mechanisms are not fully understood. To mimic increased expression of Nrg1, a schizophrenia susceptibility gene in GABAergic interneurons from patients with schizophrenia, we generated gtoNrg1 mice with overexpression of Nrg1 in GABAergic interneurons. gtoNrg1 mice showed cortical disinhibition at the cellular, synaptic, neural network and behavioral levels. We revealed that the intracellular domain of NRG1 interacts with the cytoplasmic loop 1 of Nav1.1, a sodium channel critical for the excitability of GABAergic interneurons, and inhibits Nav currents. Intriguingly, activation of GABAergic interneurons or restoring NRG1 expression in adulthood could rescue the hyperactivity and impaired social novelty in gtoNrg1 mice. These results identify mechanisms underlying cortical disinhibition related to schizophrenia and raise the possibility that restoration of NRG1 signaling and GABAergic function is beneficial in certain neuropsychiatric disorders.
This work was supported by grants from National Natural Science Foundation of China (No. 81471118 and 31861143033); grants from Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500); grants from State Key Laboratory of Neuroscience. Dr. Dong-Min Yin is a NARSAD Young Investigator.
The link of the paper is as follows: https://www.nature.com/articles/s41467-020-20552-y
Source: School of Life Science
Copy editor:Yin Dongmin