Cesa Roberta, Morando Laura, Strata Piergiorgio
Rita Levi Montalcini Center for Brain Repair, Department of Neuroscience, University of Turin, 10125 Torino, Italy.
J Neurosci. 2003 Mar 15;23(6):2363-70. doi: 10.1523/JNEUROSCI.23-06-02363.2003.
In the adult cerebellum, the glutamate receptor delta2 subunit (GluRdelta2) is selectively targeted to the spines of the distal Purkinje cell dendrites, the spiny branchlets, that are innervated by the parallel fibers. Although GluRdelta2 has no known channel function, it is presumed to be involved in the formation and stabilization of these synapses. After block of electrical activity by tetrodotoxin, GluRdelta2s appear in the postsynaptic densities of the proximal dendritic spines, which then lose their contact with climbing fibers and become ectopically innervated by parallel fibers. This phenomenon suggests that climbing fiber activity prevents GluRdelta2 targeting to proximal dendrites and that GluRdelta2s admitted to the postsynaptic density of the spine cause withdrawal of the silent climbing fiber. To test this hypothesis, we studied the distribution of GluRdelta2s in the rat cerebellum by immunoelectron microscopy during the recovery period that follows removal of the electrical block, and during the sprouting of climbing fibers that follows subtotal deletion of the parent inferior olivary neurons by administration of the drug 3-acetylpyridine. We found that after removal of the electrical block, the climbing fibers reinnervate proximal spines that bear GluRdelta2s and these subunits are successively repressed. Similarly, after subtotal lesion of the inferior olive, reinnervation of denervated Purkinje cells occurs on spines bearing GluRdelta2s. Thus, GluRdelta2s are not responsible for displacing silent climbing fibers. We propose instead that GluRdelta2s are associated with climbing fiber-to-Purkinje cell synapses, during development or at early stages of climbing fiber regeneration or sprouting, and are downregulated during the process of synapse maturation.
在成年小脑，谷氨酸受体δ2亚基（GluRδ2）选择性地定位于浦肯野细胞远端树突棘，即由平行纤维支配的棘状小分支上。尽管GluRδ2没有已知的通道功能，但推测它参与这些突触的形成和稳定。用河豚毒素阻断电活动后，GluRδ2出现在近端树突棘的突触后致密物中，这些树突棘随后失去与攀缘纤维的联系，并被平行纤维异位支配。这种现象表明，攀缘纤维活动可阻止GluRδ2定位于近端树突，而进入棘突突触后致密物的GluRδ2会导致沉默攀缘纤维退缩。为了验证这一假设，我们通过免疫电子显微镜研究了大鼠小脑在解除电阻断后的恢复期以及在用药物3 - 乙酰吡啶使下橄榄核神经元大部分缺失后攀缘纤维发芽期间GluRδ2的分布。我们发现，解除电阻断后，攀缘纤维重新支配带有GluRδ2的近端棘突，这些亚基随后被相继抑制。同样，在下橄榄核大部分损伤后，去神经支配的浦肯野细胞在带有GluRδ2的棘突上发生重新支配。因此，GluRδ2并非导致沉默攀缘纤维移位的原因。相反，我们提出GluRδ2在发育过程中或在攀缘纤维再生或发芽的早期阶段与攀缘纤维 - 浦肯野细胞突触相关联，并在突触成熟过程中被下调。
