GluRdelta2 expression in the mature cerebellum of hotfoot mice promotes parallel fiber synaptogenesis and axonal competition.
GluRdelta2 expression in the mature cerebellum of hotfoot mice promotes parallel fiber synaptogenesis and axonal competition.
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DOI：
10.1371/journal.pone.0005243
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Strata P
中科院分区：
文献类型：
--
作者：
Mandolesi G;Autuori E;Cesa R;Premoselli F;Cesare P;Strata P
谷氨酸受体β2(GluRδ2)选择性地表达于小脑，仅在与平行纤维接触的浦肯野细胞(PC)的脊椎中表达。虽然它的结构类似于离子型谷氨酸受体，但它没有通道功能，其配体也是未知的。Glurδ2基因缺失的小鼠，如基因敲除和HotFoot，已经深刻地改变了小脑电路，导致共济失调和运动学习障碍。值得注意的是，PC-PF突触中的Glurδ2调节其成熟和增强，并诱导长期抑制(LTD)。此外，GLURδ2参与了PC的两个兴奋性输入之间的高度地域性竞争：支配近端树突间的攀升纤维(CF)和连接到多刺远端小枝的PF。最近的研究表明，Glurδ2在PF的突触发生中起着黏附分子的作用。在这里，我们提供了支持这一假说的体内和体外证据。通过慢病毒抢救HotFoot小鼠，我们注意到PC-PF接触在远端树突域恢复。在近端区域，我们观察到PFS支配的新棘突的形成和与CF接触的减少，即PC的神经支配模式向Pf输入转移。此外，Glurδ2在与颗粒细胞共培养的HEK2 93细胞或成熟脑内的小脑高尔基细胞中的异位表达诱导了新的PF接触的形成。综上所述，我们的观察表明，Glurδ2是一种黏附分子，它独立于细胞定位诱导PF接触的形成，并促进PC近端树突状结构域的异突触竞争。
Glutamate receptor delta 2 (GluRδ2) is selectively expressed in the cerebellum, exclusively in the spines of the Purkinje cells (PCs) that are in contact with parallel fibers (PFs). Although its structure is similar to ionotropic glutamate receptors, it has no channel function and its ligand is unknown. The GluRδ2-null mice, such as knockout and hotfoot have profoundly altered cerebellar circuitry, which causes ataxia and impaired motor learning. Notably, GluRδ2 in PC-PF synapses regulates their maturation and strengthening and induces long term depression (LTD). In addition, GluRδ2 participates in the highly territorial competition between the two excitatory inputs to the PC; the climbing fiber (CF), which innervates the proximal dendritic compartment, and the PF, which is connected to spiny distal branchlets. Recently, studies have suggested that GluRδ2 acts as an adhesion molecule in PF synaptogenesis. Here, we provide in vivo and in vitro evidence that supports this hypothesis. Through lentiviral rescue in hotfoot mice, we noted a recovery of PC-PF contacts in the distal dendritic domain. In the proximal domain, we observed the formation of new spines that were innervated by PFs and a reduction in contact with the CF; ie, the pattern of innervation in the PC shifted to favor the PF input. Moreover, ectopic expression of GluRδ2 in HEK293 cells that were cocultured with granule cells or in cerebellar Golgi cells in the mature brain induced the formation of new PF contacts. Collectively, our observations show that GluRδ2 is an adhesion molecule that induces the formation of PF contacts independently of its cellular localization and promotes heterosynaptic competition in the PC proximal dendritic domain.
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