Neuronal heterotopias affect the activities of distant brain areas and lead to behavioral deficits

Kazuhiro Ishii, Ken Ichiro Kubo, Toshihiro Endo, Keitaro Yoshida, Seico Benner, Yukiko Ito, Hidenori Aizawa, Michihiko Aramaki, Akihiro Yamanaka, Kohichi Tanaka, Norio Takata, Kenji F. Tanaka, Masaru Mimura, Chiharu Tohyama, Masaki Kakeyama, Kazunori Nakajima

    Research output: Contribution to journalArticle

    21 Citations (Scopus)

    Abstract

    Neuronal heterotopia refers to brain malformations resulting from deficits of neuronal migration. Individuals with heterotopias show a high incidence of neurological deficits, such as epilepsy. More recently, it has come to be recognized that focal heterotopiasmayalso show a range of psychiatric problems, including cognitive and behavioral impairments. However, because focal heterotopias are not always located in the brain areas responsible for the symptoms, the causal relationship between the symptoms and heterotopias remains elusive. In this study, we showed that mice with focal heterotopias in the somatosensory cortex generated by in utero electroporation exhibited spatial working memory deficit and low competitive dominance behavior, which have been shown to be closely associated with the activity of the medial prefrontal cortex (mPFC) in rodents. Analysis of the mPFC activity revealed that the immediate-early gene expression was decreased and the local field potentials of the mPFC were altered in the mice with heterotopias compared with the control mice. Moreover, activation of these ectopic and overlying sister neurons using the DREADD (designer receptor exclusively activated by designer drug) system improved the working memory deficits. These findings suggest that cortical regions containing focal heterotopias can affect distant brain regions and give rise to behavioral abnormalities.

    Original languageEnglish
    Pages (from-to)12432-12445
    Number of pages14
    JournalJournal of Neuroscience
    Volume35
    Issue number36
    DOIs
    Publication statusPublished - 2015 Sep 9

    Keywords

    • DREADD
    • Heterotopia
    • In utero electroporation
    • IntelliCage
    • Neuropsychiatric symptom
    • Optogenetics

    ASJC Scopus subject areas

    • Neuroscience(all)

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  • Cite this

    Ishii, K., Kubo, K. I., Endo, T., Yoshida, K., Benner, S., Ito, Y., Aizawa, H., Aramaki, M., Yamanaka, A., Tanaka, K., Takata, N., Tanaka, K. F., Mimura, M., Tohyama, C., Kakeyama, M., & Nakajima, K. (2015). Neuronal heterotopias affect the activities of distant brain areas and lead to behavioral deficits. Journal of Neuroscience, 35(36), 12432-12445. https://doi.org/10.1523/JNEUROSCI.3648-14.2015