Neuronal activity is required for the development of specific cortical interneuron subtypes.
Neuronal activity is required for the development of specific cortical interneuron subtypes.
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DOI：
10.1038/nature09865
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发表时间：
2011-04-21
期刊：
影响因子：
64.8
通讯作者：
Fishell, Gord
中科院分区：
文献类型：
--
作者：
Garcia, Natalia V. De Marco;Karayannis, Theofanis;Fishell, Gord
电活动已被证明可以调节各种物种和各种结构的发育，包括视网膜、脊髓和皮质。特别是在哺乳动物的皮质中，锥体细胞中树突和连合轴突的发育是活动依赖性的。然而，很少有人知道的其他主要皮质神经元，GABA产生的中间神经元的活动的发展作用。这些神经元在形态和功能上是异质的，过去十年的努力集中在确定有助于这种多样性的机制上。最近发现，30%的皮质中间神经元来自腹侧端脑内的一个相对新颖的来源，尾侧神经节隆起（CGE）。由于它们的出生日期较晚，这些中间神经元只有在大多数其他中间神经元和锥体细胞已经就位并开始功能整合之后才能填充皮层。在这里，我们证明了在小鼠中，CGE衍生的reelin（Re）阳性和calretinin（Cr）阳性（但不是血管活性肠肽（VIP）阳性）interneurons，，活性是必不可少的出生后第3天之前正确的迁移，出生后第3天，谷氨酸介导的活动控制其轴突和树突的发展。此外，我们发现，吞噬和细胞运动1基因（Elmo 1），转录因子远端的同源异型框1（Dlx 1）的目标，选择性地表达在Re+和Cr+interneurons和活动依赖性interneurons迁移是必要的和足够的。我们的研究结果揭示了在塑造特定的神经元亚型的皮质整合活动的选择性要求。
Electrical activity has been shown to regulate development in a variety of species and in various structures, including the retina,,, spinal cord,and cortex. Within the mammalian cortex specifically, the development of dendrites and commissural axons in pyramidal cells is activity-dependent,. However, little is known about the developmental role of activity in the other major cortical population of neurons, the GABA-producing interneurons. These neurons are morphologically and functionally heterogeneous and efforts over the past decade have focused on determining the mechanisms that contribute to this diversity,,. It was recently discovered that 30% of all cortical interneurons arise from a relatively novel source within the ventral telencephalon, the caudal ganglionic eminence (CGE),. Owing to their late birth date, these interneurons populate the cortex only after the majority of other interneurons and pyramidal cells are already in place and have started to functionally integrate. Here we demonstrate in mice that for CGE-derived reelin (Re)-positive and calretinin (Cr)-positive (but not vasoactive intestinal peptide (VIP)-positive) interneurons,, activity is essential before postnatal day 3 for correct migration, and that after postnatal day 3, glutamate-mediated activity controls the development of their axons and dendrites. Furthermore, we show that the engulfment and cell motility 1 gene (Elmo1), a target of the transcription factor distal-less homeobox 1 (Dlx1), is selectively expressed in Re+and Cr+interneurons and is both necessary and sufficient for activity-dependent interneuron migration. Our findings reveal a selective requirement for activity in shaping the cortical integration of specific neuronal subtypes.
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