Inversed Effects of Nav1.2 Deficiency at Medial Prefrontal Cortex and Ventral Tegmental Area for Prepulse Inhibition in Acoustic Startle Response

Toshimitsu Suzuki, Satoko Hattori, Hiroaki Mizukami, Ryuichi Nakajima, Yurina Hibi, Saho Kato, Mahoro Matsuzaki, Ryu Ikebe, Tsuyoshi Miyakawa, Kazuhiro Yamakawa

Research output: Contribution to journalArticlepeer-review

Abstract

Numerous pathogenic variants of SCN2A gene, encoding voltage-gated sodium channel α2 subunit Nav1.2 protein, have been identified in a wide spectrum of neuropsychiatric disorders including schizophrenia. However, pathological mechanisms for the schizophrenia-relevant behavioral abnormalities caused by the variants remain poorly understood. Here in this study, we characterized mouse lines with selective Scn2a deletion at schizophrenia-related brain regions, medial prefrontal cortex (mPFC) or ventral tegmental area (VTA), obtained by injecting adeno-associated viruses (AAV) expressing Cre recombinase into homozygous Scn2a-floxed (Scn2afl/fl) mice, in which expression of the Scn2a was locally deleted in the presence of Cre recombinase. The mice lacking Scn2a in the mPFC exhibited a tendency for a reduction in prepulse inhibition (PPI) in acoustic startle response. Conversely, the mice lacking Scn2a in the VTA showed a significant increase in PPI. We also found that the mice lacking Scn2a in the mPFC displayed increased sociability, decreased locomotor activity, and increased anxiety-like behavior, while the mice lacking Scn2a in the VTA did not show any other abnormalities in these parameters except for vertical activity which is one of locomotor activities. These results suggest that Scn2a-deficiencies in mPFC and VTA are inversely relevant for the schizophrenic phenotypes in patients with SCN2A variants.

Original languageEnglish
Pages (from-to)622-634
Number of pages13
JournalMolecular Neurobiology
Volume61
Issue number2
DOIs
Publication statusPublished - 02-2024

All Science Journal Classification (ASJC) codes

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

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