Ablation of ErbB4 from excitatory neurons leads to reduced dendritic spine density in mouse prefrontal cortex.
Ablation of ErbB4 from excitatory neurons leads to reduced dendritic spine density in mouse prefrontal cortex.
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DOI：
10.1002/cne.23615
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发表时间：
2014-10-01
影响因子：
2.5
通讯作者：
Koleske, Anthony J.
中科院分区：
文献类型：
--
作者：
Cooper, Margaret A.;Koleske, Anthony J.
树突棘缺失在许多精神疾病中观察到，包括精神分裂症，并且可能导致现实感改变，工作记忆中断和注意力缺陷，这些疾病是这些疾病的特征。ErbB4是EGF受体酪氨酸激酶家族的一员，与精神分裂症有遗传相关性，提示ErbB4功能的改变与疾病病理有关。此外，ErbB4在突触可塑性中发挥作用，这使我们假设ErbB4信号传导的中断可能会影响树突棘的发育。我们发现，树突棘密度减少，在背内侧前额叶皮质的ErbB4条件性全脑敲除小鼠。我们发现，ErbB4定位于皮层神经元培养的兴奋性神经元的树突棘，并存在于突触质膜制剂。最后，我们证明，选择性消融ErbB4兴奋性神经元导致的比例下降，成熟的棘和整体减少树突棘密度在前额叶皮层的断奶（P21）小鼠，持续在2个月的年龄。这些结果表明，兴奋性锥体细胞中的ErbB4信号传导对于兴奋性锥体细胞中树突棘的正确形成和维持至关重要。
Dendritic spine loss is observed in many psychiatric disorders, including schizophrenia, and likely contributes to the altered sense of reality, disruption of working memory, and attention deficits that characterize these disorders. ErbB4, a member of the EGF family of receptor tyrosine kinases, is genetically associated0020with schizophrenia, suggesting that alterations in ErbB4 function contribute to the disease pathology. Additionally, ErbB4 functions in synaptic plasticity, leading us to hypothesize that disruption of ErbB4 signaling may affect dendritic spine development. We show that dendritic spine density is reduced in the dorsomedial prefrontal cortex of ErbB4 conditional whole-brain knockout mice. We find that ErbB4 localizes to dendritic spines of excitatory neurons in cortical neuronal cultures and is present in synaptic plasma membrane preparations. Finally, we demonstrate that selective ablation of ErbB4 from excitatory neurons leads to a decrease in the proportion of mature spines and an overall reduction in dendritic spine density in the prefrontal cortex of weanling (P21) mice that persists at 2 months of age. These results suggest that ErbB4 signaling in excitatory pyramidal cells is critical for the proper formation and maintenance of dendritic spines in excitatory pyramidal cells.
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影响因子：
3.3
作者：
Glausier, J. R.;Lewis, D. A.
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.1010669107
发表时间：
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影响因子：
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