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Front. Mol. Neurosci. | doi: 10.3389/fnmol.2019.00145

Scn2a haploinsufficiency in mice suppresses hippocampal neuronal excitability, excitatory synaptic drive, and long-term potentiation, and spatial learning and memory

Wangyong Shin1,  Hanseul Kweon1, Ryeonghwa Kang1, Doyoun Kim2, Kyungdeok Kim1, Muwon Kang1, Seo Yeong Kim1, Sun Nam Hwang2,  Jin Yong Kim3, Esther Yang3,  Hyun Kim3 and  Eunjoon Kim1, 2*
  • 1Korea Advanced Institute of Science & Technology (KAIST), South Korea
  • 2Institute for Basic Science (IBS), South Korea
  • 3College of Medicine, Korea University, South Korea

Nav1.2, a voltage-gated sodium channel subunit encoded by the Scn2a gene, has been implicated in various brain disorders, including epilepsy, autism spectrum disorder, intellectual disability, and schizophrenia. Nav1.2 is known to regulate the generation of action potentials in the axon initial segment and their propagation along axonal pathways. Nav1.2 also regulates synaptic integration and plasticity by promoting back-propagation of action potentials to dendrites, but whether Nav1.2 deletion in mice affects neuronal excitability, synaptic transmission, synaptic plasticity, and/or disease-related animal behaviors remains largely unclear. Here we report that mice heterozygous for the Scn2a gene (Scn2a+/– mice) show decreased neuronal excitability and suppressed excitatory synaptic transmission in the presence of network activity in the hippocampus. In addition, Scn2a+/– mice show suppressed hippocampal long-term potentiation in association with impaired spatial learning and memory, but show largely normal locomotor activity, anxiety-like behavior, social interaction, repetitive behavior, and whole-brain excitation. These results suggest that Nav1.2 regulates hippocampal neuronal excitability, excitatory synaptic drive, long-term potentiation, and spatial learning and memory in mice.

Keywords: Sodium channel, Neuronal excitability, Synaptic Transmission, synaptic plasticity, learning and memory, Autism (ASD), Intellectual disabilities (ID), Schizophrenia

Received: 11 Apr 2019; Accepted: 17 May 2019.

Edited by:

Yi-Ping Hsueh, Institute of Molecular Biology, Academia Sinica, Taiwan

Reviewed by:

Hyunsoo S. JE, Duke-NUS Medical School, Singapore
Carlo Sala, Institute of Neuroscience (IN), Italy  

Copyright: © 2019 Shin, Kweon, Kang, Kim, Kim, Kang, Kim, Hwang, Kim, Yang, Kim and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Eunjoon Kim, Institute for Basic Science (IBS), Daejeon, South Korea, kime@kaist.ac.kr