Development of axon-target specificity of ponto-cerebellar afferents.
Development of axon-target specificity of ponto-cerebellar afferents.
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DOI：
10.1371/journal.pbio.1001013
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发表时间：
2011-02-08
期刊：
影响因子：
9.8
通讯作者：
Scheiffele P
中科院分区：
文献类型：
--
作者：
Kalinovsky A;Boukhtouche F;Blazeski R;Bornmann C;Suzuki N;Mason CA;Scheiffele P
神经网络的功能依赖于发育过程中突触连接的选择性组装。我们研究了脑桥小脑投射中突触特异性是如何产生的。通过相关的光镜 - 电镜对轴突 - 靶标相互作用的分析显示，发育中的脑桥苔藓纤维与浦肯野细胞（一个不恰当的靶标）形成了广泛的细胞 - 细胞接触和突触连接。随后，苔藓纤维 - 浦肯野细胞连接被消除，从而形成了在成熟小脑回路中所观察到的颗粒细胞特异性苔藓纤维连接。苔藓纤维 - 浦肯野细胞接触的形成受到浦肯野细胞衍生的骨形态发生蛋白4（BMP4）的负调控。BMP4在体外限制苔藓纤维的生长，并且在小鼠中对浦肯野细胞特异性地去除BMP4会导致苔藓纤维 - 浦肯野细胞相互作用过度。这些发现表明，脑桥小脑投射中的突触特异性是通过一种逐步的机制实现的，该机制包括浦肯野细胞的短暂神经支配，随后是突触消除。此外，这项工作确立了BMP4作为一种逆行信号，在发育过程中调节轴突 - 靶标相互作用。
大脑功能依赖于在发育过程中组装的高度选择性的神经网络。网络组装包括定向的神经元生长，随后是对恰当靶细胞的识别以及选择性突触形成。神经元突起如何从一系列相互作用的伙伴中选择其恰当的靶细胞，人们对此知之甚少。在这项研究中，我们针对从脑桥灰质核发出的轴突探讨了这个问题，脑桥灰质核是一个主要的脑干核，它在大脑皮层和小脑之间传递信息，小脑是一个负责控制熟练运动以及情绪处理的脑区。利用先进的显微镜技术，我们发现发育中的苔藓纤维相当杂乱地建立突触接触，并与浦肯野细胞（一个不恰当的靶标）形成广泛的突触。这些接触随后被消除，恰当的突触连接随后被限制在颗粒细胞和高尔基神经元。我们确定骨形态发生蛋白4（BMP4）是这些不恰当的苔藓纤维 - 浦肯野细胞接触的一个调节因子。BMP生长因子最为人所知的是它们在胚胎发育过程中细胞特化方面的功能，我们的结果支持了在出生后早期阶段轴突与其靶细胞之间的一种额外的逆行信号传递功能。总之，我们表明脑桥 - 小脑回路中突触连接的特异性是通过广泛消除短暂突触而产生的。
The function of neuronal networks relies on selective assembly of synaptic connections during development. We examined how synaptic specificity emerges in the pontocerebellar projection. Analysis of axon-target interactions with correlated light-electron microscopy revealed that developing pontine mossy fibers elaborate extensive cell-cell contacts and synaptic connections with Purkinje cells, an inappropriate target. Subsequently, mossy fiber–Purkinje cell connections are eliminated resulting in granule cell-specific mossy fiber connectivity as observed in mature cerebellar circuits. Formation of mossy fiber-Purkinje cell contacts is negatively regulated by Purkinje cell-derived BMP4. BMP4 limits mossy fiber growth in vitro and Purkinje cell-specific ablation of BMP4 in mice results in exuberant mossy fiber–Purkinje cell interactions. These findings demonstrate that synaptic specificity in the pontocerebellar projection is achieved through a stepwise mechanism that entails transient innervation of Purkinje cells, followed by synapse elimination. Moreover, this work establishes BMP4 as a retrograde signal that regulates the axon-target interactions during development. Brain functions rely on highly selective neuronal networks which are assembled during development. Network assembly involves targeted neuronal growth followed by recognition of the appropriate target cells and selective synapse formation. How neuronal processes select their appropriate target cells from an array of interaction partners is poorly understood. In this study, we have addressed this question for the axons emerging from the pontine gray nucleus, a major brainstem nucleus that relays information between the cortex and the cerebellum, a brain area responsible for the control of skilled movements but also emotional processing. Using advanced microscopy techniques, we find that developing mossy fibers establish synaptic contacts rather promiscuously, and elaborate extensive synapses with Purkinje cells, an inappropriate target. These contacts are subsequently eliminated, and proper synaptic connectivity is then restricted to granule and Golgi neurons. We identify bone morphogenetic protein 4 (BMP4) as a regulator of these inappropriate mossy fiber-Purkinje cell contacts. BMP growth factors are best known for their functions in cell specification during embryonic development, and our results support an additional retrograde signaling function between axons and their target cells in early postnatal stages. In summary, we show that the specificity of the synaptic connections in the ponto-cerebellar circuit emerges through extensive elimination of transient synapses.
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影响因子：
3.3
作者：
通讯作者：
--
DOI：
10.1002/neu.1046
发表时间：
2001-08-01
期刊：
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影响因子：
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通讯作者：
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影响因子：
4.5
作者：
Chang, Weise;Lin, Zhengshi;Kulessa, Holger;Hebert, Jean;Hogan, Brigid L. M.;Wu, Doris K.
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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