Maturation of "Neocortex Isole" In Vivo in Mice
Maturation of "Neocortex Isole" In Vivo in Mice
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DOI：
10.1523/jneurosci.6005-09.2010
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发表时间：
2010-06-09
影响因子：
5.3
通讯作者：
Goffinet, Andre M.
中科院分区：
文献类型：
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作者：
Zhou, Libing;Gall, David;Goffinet, Andre M.
新皮质的发育在多大程度上依赖于连接仍然是个谜。在这里，我们发现 Celsr3 垂直杆 Dlx 突变小鼠没有外在的新皮质连接，但仍能存活到出生后 20 天，获得基本的行为能力，并表现出自发性多动，伴有异常的光/暗活动循环。除了与丘脑输入相关的特征（例如体感皮层中的桶）外，皮层区域化和层状成熟均正常进行。然而，成熟皮质的切向延伸减少了，径向厚度受到的影响较小。深层神经元数量减少，其顶端和基底树突乔木变钝，突触密度降低。中间神经元到达皮质，其密度与野生型相当。在急性切片的膜片钳实验中体外测量的突变锥体神经元的兴奋性降低。然而，除了一些突变神经元存在快速放电衰竭之外，它们的体内放电活性与野生型非常相似。局部场电位和皮质电图显示出相似的振荡范围，尽管突变体的频率峰值更高并且左右同步性降低。因此，“原型图”的形成，即皮质分层和区域化，在没有外部连接的情况下正常进行，但投射神经元的存活以及成熟形态和一些电生理特征的获得取决于正常皮质-皮质下关系的建立。
How much neocortical development depends on connections remains elusive. Here, we show that Celsr3 vertical bar Dlx mutant mice have no extrinsic neocortical connections yet survive to postnatal day 20, acquire a basic behavioral repertoire, and display spontaneous hyperactivity, with abnormal light/dark activity cycling. Except for hallmarks related to thalamic input, such as barrels in somatosensory cortex, cortical arealization and laminar maturation proceeded normally. However, the tangential extension of the mature cortex was diminished, with radial thickness less severely affected. Deep layer neurons were reduced in number, and their apical and basal dendritic arbors were blunted, with reduced synapse density. Interneurons reached the cortex, and their density was comparable with wild type. The excitability of mutant pyramidal neurons, measured in vitro in patch-clamp experiments in acute slices, was decreased. However, their firing activity in vivo was quite similar to the wild type, except for the presence of rapid firing exhaustion in some mutant neurons. Local field potential and electrocorticogram showed similar range of oscillations, albeit with higher frequency peaks and reduced left-right synchrony in the mutant. Thus, "protomap" formation, namely cortical lamination and arealization, proceed normally in absence of extrinsic connections, but survival of projection neurons and acquisition of mature morphological and some electrophysiological features depend on the establishment of normal cortical-subcortical relationships.