Washington University in St. Louis

New Publication for Klyachko Lab

Congratulations to Panyue Deng and Vitaly Klyachko on their publication in Cell Reports!  

Deng, P and Klyachko, VA (2016) Increased Persistent Sodium Current Causes Neuronal Hyperexcitability in the Entorhinal Cortex of Fmr! Knockout Mice, Cell Rep, 16(12):3157-3166.

Abstract:  Altered neuronal excitability is one of the hallmarks of fragile X syndrome (FXS), but the mechanisms underlying this critical neuronal dysfunction are poorly understood. Here, we find that pyramidal cells in the entorhinal cortex of Fmr1 KO mice, an established FXS mouse model, display a decreased AP threshold and increased neuronal excitability. The AP threshold changes in Fmr1 KO mice are caused by increased persistent sodium current (INaP). Our results indicate that this abnormal INaP in Fmr1 KO animals is mediated by increased mGluR5-PLC-PKC (metabotropic glutamate receptor 5/phospholipase C/protein kinase C) signaling. These findings identify Na(+) channel dysregulation as a major cause of neuronal hyperexcitability in cortical FXS neurons and uncover a mechanism by which abnormal mGluR5 signaling causes neuronal hyperexcitability in a FXS mouse model.

 

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