Synapse elimination and learning rules co-regulated by MHC class I H2-D-b

Article

关键词: LONG-TERM DEPRESSION;    AMPA RECEPTORS;    RETINAL WAVES;    RETINOGENICULATE;    PLASTICITY;    LTP;    CNS;    TRANSMISSION;    SEGREGATION;    REQUIREMENT;   

DOI  :  10.1038/nature13154

来源: SCIE

【 摘 要 】

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-D-b is necessary and sufficient for synapse elimination in the retinogeniculate system. In mice lacking both H2-K-b and H2-D-b ((KDb-/-)-D-b), 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 (KDb-/-)-D-b 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 (KDb-/-)-D-b mice. This change is due to an increase in Ca2+-permeable AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Restoring H2-D-b to (KDb-/-)-D-b 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-D-b in functional and structural synapse pruning in CNS neurons.

【 授权许可】

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