Nicotinic α5 Subunits Drive Developmental Changes in the Activation and Morphology of Prefrontal Cortex Layer VI Neurons
Nicotinic α5 Subunits Drive Developmental Changes in the Activation and Morphology of Prefrontal Cortex Layer VI Neurons
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DOI：
10.1016/j.biopsych.2011.09.011
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发表时间：
2012-01-15
影响因子：
10.6
通讯作者：
Lambe, Evelyn K.
中科院分区：
文献类型：
--
作者：
Bailey, Craig D. C.;Alves, Nyresa C.;Lambe, Evelyn K.
背景：前额叶第VI层锥体神经元的烟碱信号对成熟注意系统的功能具有重要作用。α 5亚基正常掺入α 4 β 2* 烟碱乙酰胆碱受体增强了这些神经元中的烟碱信号传导，并且是成年小鼠正常注意力表现所需的。然而，α 5亚基在前额叶皮层发育中的作用尚不清楚。方法：我们试图通过检测野生型和α 5亚基敲除的内侧前额叶皮层第VI层神经元的烟碱电流和神经元形态来回答这个问题。（α 5（-/-））小鼠在出生后发育和成年期。在野生型，但不是在α 5（-/-）小鼠，有一个发育高峰，烟碱乙酰胆碱电流在出生后第三周。在这个幼年时期，所有小鼠中的大多数神经元具有延伸到皮层I层的长的顶端树突。然而，在成年早期，野生型而不是α 5（-/-）小鼠显示出明显的向较短的顶端树突的转变。这种细胞的差异发生在没有基因型差异在整体cortical morphology.Conclusions：正常的发育变化，烟碱信号和树突状形态在前额皮质依赖于α 5-包括烟碱乙酰胆碱受体。看来，这些受体介导的第VI层神经元中的顶端树突的特定发育收缩。这一发现提供了新的见解，潜在的细胞机制，在阿尔法5（-/-）小鼠的注意力缺陷和潜在的发展神经精神障碍，如注意力缺陷障碍和自闭症的病理生理。
Background: Nicotinic signaling in prefrontal layer VI pyramidal neurons is important to the function of mature attention systems. The normal incorporation of alpha 5 subunits into alpha 4 beta 2* nicotinic acetylcholine receptors augments nicotinic signaling in these neurons and is required for normal attention performance in adult mice. However, the role of alpha 5 subunits in the development of the prefrontal cortex is not known.Methods: We sought to answer this question by examining nicotinic currents and neuronal morphology in layer VI neurons of medial prefrontal cortex of wild-type and alpha 5 subunit knockout (alpha 5(-/-)) mice during postnatal development and in adulthood.Results: In wild-type but not in alpha 5(-/-) mice, there is a developmental peak in nicotinic acetylcholine currents in the third postnatal week. At this juvenile time period, the majority of neurons in all mice have long apical dendrites extending into cortical layer I. Yet, by early adulthood, wild-type but not alpha 5(-/-) mice show a pronounced shift toward shorter apical dendrites. This cellular difference occurs in the absence of genotype differences in overall cortical morphology.Conclusions: Normal developmental changes in nicotinic signaling and dendritic morphology in prefrontal cortex depend on alpha 5-comprising nicotinic acetylcholine receptors. It appears that these receptors mediate a specific developmental retraction of apical dendrites in layer VI neurons. This finding provides novel insight into the cellular mechanisms underlying the known attention deficits in alpha 5(-/-) mice and potentially also into the pathophysiology of developmental neuropsychiatric disorders such as attention-deficit disorder and autism.