TrkB signaling regulates the developmental maturation of the somatosensory cortex
TrkB signaling regulates the developmental maturation of the somatosensory cortex
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DOI：
10.1016/j.ijdevneu.2005.04.003
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发表时间：
2005-10-01
影响因子：
1.8
通讯作者：
Parada, LF
中科院分区：
文献类型：
--
作者：
Lush, ME;Ma, L;Parada, LF
在啮齿类动物的中枢神经系统中，对面部须刺激做出反应的皮层区域在解剖学上被划分为称为“桶”的离散区域。每个桶由第四层皮层神经元组成，这些神经元通过丘脑的神经支配接收来自单独须的输入。研究表明，神经营养物质在丘脑轴突神经支配的发育和可塑性中起着重要作用。我们现在将这些发现扩展到神经营养因子信号在桶状皮层形成中的作用的研究。我们发现神经营养因子受体TrkB在皮层神经支配期间在丘脑和皮层表达。两种TrkB配体，脑源性神经营养因子（BDNF）和神经营养因子-4 (NT-4)，此时在皮质中表达。缺乏TrkB的小鼠表现出丘脑轴突在桶内分离的发育延迟。在Trkl3突变体中，与对照组相比，在出生后第4天，丘脑轴突在皮层第四层内异常均匀，但在2天后显示出明显的桶状分离。这种表型在BDNF突变小鼠中重现，但在NT-4突变小鼠中没有。这些结果表明BDNF是唯一负责这种表型的Trkl3配体。对在皮层而非丘脑中缺乏TrkB的条件敲除小鼠的分析，没有显示丘脑轴突分离的延迟。这些结果表明TrkB在丘脑轴突的表达对于桶状皮质发育的适当时机至关重要。(c) 2005综合业务网络。Elsevier Ltd.出版。版权所有。
In the rodent central nervous system, the region of the cortex that responds to facial whisker stimulation is anatomically segregated into discrete regions called barrels. Each barrel is made up of layer IV cortical neurons that receive input from a separate whisker via innervation from the thalamus. It has been shown that neurotrophins play important roles in the development and plasticity of thalamic axon innervation into the visual and retrosplenial cortex. We now extend those findings to the investigation of the role of neurotrophin signaling in barrel cortex formation. We show that the neurotrophin receptor TrkB is expressed in the thalamus and cortex during the time of cortical innervation. The two TrkB ligands, brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4), are expressed in the cortex at this time. Mice lacking TrkB demonstrate a developmental delay in the segregation of thalamic axons within barrels. In Trkl3 mutants, thalamic axons are abnormally uniform within layer IV of the cortex at postnatal day 4 compared to their control littermates, but show clear segregation into barrels 2 days later. This phenotype is recapitulated in BDNF mutant mice, but not in NT-4 mutant mice. These results demonstrate that BDNF is the sole Trkl3 ligand responsible for this phenotype. Analysis of conditional knockout mice that lack TrkB within the cortex, and not the thalamus, does not show a delay in thalamic axon segregation. These results indicate that TrkB expression in thalamic axons is important for the appropriate timing of barrel cortex development. (c) 2005 ISDN. Published by Elsevier Ltd. All rights reserved.