mGluR5 Regulates Glutamate-Dependent Development of the Mouse Somatosensory Cortex
mGluR5 Regulates Glutamate-Dependent Development of the Mouse Somatosensory Cortex
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DOI：
10.1523/jneurosci.2600-08.2008
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发表时间：
2008-12-03
影响因子：
5.3
通讯作者：
Kind, Peter C.
中科院分区：
文献类型：
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作者：
Wijetunge, Lasani S.;Till, Sally M.;Kind, Peter C.
我们之前曾报道过，mGluR5 信号通过 PLC-beta 1 调节小鼠 S1（桶状）皮质内胡须模式的发育（Hannan 等人，2001）。然而，这些缺陷是否是由于突触后 mGluR5 信号传导的缺失引起的，以及 mGluR5 的水平是否对桶形形成很重要，尚未得到检验。此外，mGluR5 是否调节桶状发育之前或之后发生的其他发育过程尚不清楚。我们现在表明，在桶形成过程中，mGluR5 存在于丘脑皮质突触的突触后。此外，Mglur5(+/-) 小鼠表现出正常的 TCA 斑块形成，但第 4 层的细胞分离减少，表明 mGluR5 在模式形成调节中的剂量依赖性作用。此外，Mglur5(-/-) 和 Mglur5(+/-) 小鼠表现出正常的皮质区域化、层形成和 PMBSF 大小，表明 S1 内的缺陷不是由发育早期阶段皮质映射的一般异常引起的。与 Mglur5(-/-) 小鼠相比，在 P21 层，Mglur5(-/-) 和 Mglur5(+/-) 小鼠的第 4 层神经元表现出脊柱密度显着降低，但树突复杂性正常，表明在皮质发育过程中突触发生中发挥作用。最后，mGluR5 调节整个小鼠三叉神经系统的模式形成，因为 Mglur5(-/-) 小鼠中 PrV、VpM 和 S1 皮质中 AS 须的代表被破坏。这些数据共同表明 mGluR5 在小鼠三叉神经系统神经元发育的早期和晚期阶段发挥着关键作用。
We have previously reported that mGluR5 signaling via PLC-beta 1 regulates the development of whisker patterns within S1 (barrel) cortex of mice (Hannan et al., 2001). However, whether these defects arise from the loss of postsynaptic mGluR5 signaling, and whether the level of mGluR5 is important for barrel formation, was not examined. Furthermore, whether mGluR5 regulates other developmental processes that occur before or after barrel development is not known. We now show that mGluR5 is present postsynaptically at thalamocortical synapses during barrel formation. In addition, Mglur5(+/-) mice exhibit normal TCA patch formation but reduced cellular segregation in layer 4, indicating a dose-dependent role for mGluR5 in the regulation of pattern formation. Furthermore Mglur5(-/-) and Mglur5(+/-) mice display normal cortical arealization, layer formation, and size of PMBSF indicating the defects within S1 do not result from general abnormalities of cortical mapping during earlier stages of development. At P21 layer 4 neurons from Mglur5(-/-) and Mglur5(+/-) mice show a significant reduction in spine density but normal dendritic complexity compared with Mglur5(-/-) mice indicating a role in synaptogenesis during cortical development. Finally, mGluR5 regulates pattern formation throughout the trigeminal system of mice as the representation of the AS whiskers in the PrV, VpM, and S1 cortex was disrupted in Mglur5(-/-) mice. Together these data indicate a key role for mGluR5 at both early and late stages of neuronal development in the trigeminal system of mice.