The Cain Foundation Laboratories, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
J Neurosci. 2010 Dec 15;30(50):16896-909. doi: 10.1523/JNEUROSCI.2462-10.2010.
Glutamatergic neurotransmission plays important roles in sensory map formation. The absence of the group I metabotropic glutamate receptor 5 (mGluR5) leads to abnormal sensory map formation throughout the mouse somatosensory pathway. To examine the role of cortical mGluR5 expression on barrel map formation, we generated cortex-specific mGluR5 knock-out (KO) mice. Eliminating mGluR5 function solely in cortical excitatory neurons affects, not only the whisker-related organization of cortical neurons (barrels), but also the patterning of their presynaptic partners, the thalamocortical axons (TCAs). In contrast, subcortical whisker maps develop normally in cortical-mGluR5 KO mice. In the S1 cortex of cortical-mGluR5 KO, layer IV neurons are homogenously distributed and have no clear relationship to the location of TCA clusters. The altered dendritic morphology of cortical layer IV spiny stellate neurons in cortical-mGluR5 KO mice argues for a cell-autonomous role of mGluR5 in dendritic patterning. Furthermore, morphometric analysis of single TCAs in both cortical- and global-mGluR5 KO mice demonstrated that in these mice, the complexity of axonal arbors is reduced, while the area covered by TCA arbors is enlarged. Using voltage-clamp whole-cell recordings in acute thalamocortical brain slices, we found that KO of mGluR5 from cortical excitatory neurons reduced inhibitory but not excitatory inputs onto layer IV neurons. This suggests that mGluR5 signaling in cortical excitatory neurons nonautonomously modulates the functional development of GABAergic circuits. Together, our data provide strong evidence that mGluR5 signaling in cortical principal neurons exerts both cell-autonomous and -nonautonomous influences to modulate the formation of cortical sensory circuits.
谷氨酸能神经传递在感觉图谱形成中起着重要作用。缺失 I 组代谢型谷氨酸受体 5（mGluR5）会导致小鼠整个体感通路的感觉图谱形成异常。为了研究皮质 mGluR5 表达对桶状图形成的作用，我们生成了皮质特异性 mGluR5 敲除（KO）小鼠。仅消除皮质兴奋性神经元中的 mGluR5 功能，不仅会影响与胡须相关的皮质神经元（桶状结构）的组织，还会影响其突触前伙伴——丘脑皮质轴突（TCAs）的模式形成。相比之下，皮质 mGluR5 KO 小鼠的皮质下胡须图谱正常发育。在皮质 mGluR5 KO 的 S1 皮质中，IV 层神经元均匀分布，与 TCA 簇的位置没有明显关系。皮质 mGluR5 KO 小鼠皮质 IV 层棘星状神经元的树突形态改变表明 mGluR5 在树突模式形成中具有细胞自主作用。此外，对皮质和全皮质 mGluR5 KO 小鼠的单个 TCAs 的形态计量分析表明，在这些小鼠中，轴突分支的复杂性降低，而 TCA 分支所覆盖的区域扩大。在急性丘脑皮质脑片中进行电压钳全细胞膜片记录，我们发现从皮质兴奋性神经元中敲除 mGluR5 会减少抑制性但不减少兴奋性传入到 IV 层神经元。这表明皮质兴奋性神经元中的 mGluR5 信号非自主调节 GABA 能回路的功能发育。总之，我们的数据提供了强有力的证据，表明皮质主要神经元中的 mGluR5 信号通过细胞自主和非自主的影响来调节皮质感觉回路的形成。
