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

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

Research output: Contribution to journalArticle

19 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

Fingerprint

Prefrontal Cortex
Memory Disorders
Short-Term Memory
Brain
Competitive Behavior
Designer Drugs
Immediate-Early Genes
Somatosensory Cortex
Electroporation
Psychiatry
Rodentia
Epilepsy
Gene Expression
Neurons
Incidence

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neuronal heterotopias affect the activities of distant brain areas and lead to behavioral deficits. / Ishii, Kazuhiro; Kubo, Kenichiro; Endo, Toshihiro; Yoshida, Keitaro; Benner, Seico; Ito, Yukiko; Aizawa, Hidenori; Aramaki, Michihiko; Yamanaka, Akihiro; Tanaka, Kohichi; Takata, Norio; Tanaka, Kenji; Mimura, Masaru; Tohyama, Chiharu; Kakeyama, Masaki; Nakajima, Kazunori.

In: Journal of Neuroscience, Vol. 35, No. 36, 09.09.2015, p. 12432-12445.

Research output: Contribution to journalArticle

Ishii, K, Kubo, K, Endo, T, Yoshida, K, Benner, S, Ito, Y, Aizawa, H, Aramaki, M, Yamanaka, A, Tanaka, K, Takata, N, Tanaka, K, 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, vol. 35, no. 36, pp. 12432-12445. https://doi.org/10.1523/JNEUROSCI.3648-14.2015
Ishii, Kazuhiro ; Kubo, Kenichiro ; Endo, Toshihiro ; Yoshida, Keitaro ; Benner, Seico ; Ito, Yukiko ; Aizawa, Hidenori ; Aramaki, Michihiko ; Yamanaka, Akihiro ; Tanaka, Kohichi ; Takata, Norio ; Tanaka, Kenji ; Mimura, Masaru ; Tohyama, Chiharu ; Kakeyama, Masaki ; Nakajima, Kazunori. / Neuronal heterotopias affect the activities of distant brain areas and lead to behavioral deficits. In: Journal of Neuroscience. 2015 ; Vol. 35, No. 36. pp. 12432-12445.
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