Neuronal Heterotopias Affect the Activities of Distant Brain Areas and Lead to Behavioral Deficits
Neuronal Heterotopias Affect the Activities of Distant Brain Areas and Lead to Behavioral Deficits
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DOI：
10.1523/jneurosci.3648-14.2015
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发表时间：
2015-09-09
影响因子：
5.3
通讯作者：
Nakajima, Kazunori
中科院分区：
文献类型：
--
作者：
Ishii, Kazuhiro;Kubo, Ken-ichiro;Nakajima, Kazunori
神经元异位是指由于神经元迁移障碍而导致的脑畸形。患有异位的个体表现出高发生率的神经功能缺陷，如癫痫。最近，人们认识到局灶性异位也可能表现出一系列精神问题，包括认知和行为障碍。然而，由于局灶性异位并不总是位于负责症状的大脑区域，因此症状与异位之间的因果关系仍然难以捉摸。在本研究中，我们发现子宫内电穿孔引起的体感皮层局灶性异位小鼠表现出空间工作记忆缺陷和低竞争优势行为，这与啮齿动物内侧前额叶皮层（mPFC）的活动密切相关。对mPFC活性的分析表明，与对照小鼠相比，异位小鼠mPFC的早期基因表达减少，局部场电位发生改变。此外，使用设计药物激活的设计受体（DREADD）系统激活这些异位和覆盖的姐妹神经元改善了工作记忆缺陷。这些发现表明含有局灶性异位的皮质区域可以影响远端大脑区域并引起行为异常。
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 heterotopias may also 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.