Nature2014-06-18 3:06 PM

一种MHC 分子在眼睛发育中所起作用 Synapse elimination and learning rules co-regulated by MHC class I H2-Db

论文摘要 

“主要组织相容性复合体”(MHC) class I分子H2-Db(以前被认为不在神经元中表达)在这项研究中被发现是视觉系统的发育过程中突触消除所需的。Carla Shatz及同事报告说,在缺少两个MHCI分子H2-Kb 和 H2-Db的小鼠中,确保视网膜和外侧膝状体核之间精确连接的视网膜膝状体通道中功能性和结构性突触消除都会失败。这种失败会被H2-Db在神经元中的选择性表达逆转。H2-Db在可塑性过程中也发挥功能,这表明突触消除与被改变的学习规则的共调控之间存在一个分子联系。

Abstract 

The formation of precise connections between retina and lateral geniculate nucleus (LGN) involves the activity-dependent elimination of some synapses, with strengthening and retention of others. Here we show that the major histocompatibility complex (MHC) class I molecule H2-Db is necessary and sufficient for synapse elimination in the retinogeniculate system. In mice lacking both H2-Kb and H2-Db (KbDb−/−), despite intact retinal activity and basal synaptic transmission, the developmentally regulated decrease in functional convergence of retinal ganglion cell synaptic inputs to LGN neurons fails and eye-specific layers do not form. Neuronal expression of just H2-Db in KbDb−/− mice rescues both synapse elimination and eye-specific segregation despite a compromised immune system. When patterns of stimulation mimicking endogenous retinal waves are used to probe synaptic learning rules at retinogeniculate synapses, long-term potentiation (LTP) is intact but long-term depression (LTD) is impaired in KbDb−/− mice. This change is due to an increase in Ca2+-permeable AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Restoring H2-Db to KbDb−/− neurons renders AMPA receptors Ca2+ impermeable and rescues LTD. These observations reveal an MHC-class-I-mediated link between developmental synapse pruning and balanced synaptic learning rules enabling both LTD and LTP, and demonstrate a direct requirement for H2-Db in functional and structural synapse pruning in CNS neurons.

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