CKAMP44 modulates integration of visual inputs in the lateral geniculate nucleus.
CKAMP44 modulates integration of visual inputs in the lateral geniculate nucleus.
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CKAMP44调节侧向核核中视觉输入的整合。
DOI：
10.1038/s41467-017-02415-1
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发表时间：
2018-01-17
影响因子：
16.6
通讯作者：
von Engelhardt J
中科院分区：
文献类型：
--
作者：
Chen X;Aslam M;Gollisch T;Allen K;von Engelhardt J
背外侧膝状体核（dLGN）中的中继神经元接收来自视网膜神经节细胞（RGC）的兴奋性输入。视网膜膝状体突触的特点是AMPA受体（AMPAR）介导的电流的一个突出的短期抑制，但其潜在的机制和视觉整合的功能还不清楚。在这里，我们确定CKAMP 44作为dLGN中继神经元中AMPAR的重要辅助亚基，在那里它增加AMPAR介导的电流幅度并调节AMPAR的门控。重要的是，CKAMP 44通过降低AMPAR脱敏的恢复率，负责视网膜膝状体突触中独特的短期抑制。CKAMP 44的基因缺失强烈地减少了突触的短期抑制，这导致当用来自视网膜神经突触的高频输入激活时，中继神经元的尖峰概率增加。最后，体内记录揭示了CKAMP 44敲除（CKAMP 44 −/−）小鼠中dLGN神经元的ON和OFF反应增强，证明了CKAMP 44对调节突触短期抑制和视觉输入整合的重要性。受体脱敏在体内的功能还不清楚。在这里，作者表明，CKAMP 44（一种调节AMPAR电流脱敏的AMPAR辅助蛋白）的缺失会影响清醒小鼠视网膜神经突触的突触易化和视觉诱发的放电。
Relay neurons in the dorsal lateral geniculate nucleus (dLGN) receive excitatory inputs from retinal ganglion cells (RGCs). Retinogeniculate synapses are characterized by a prominent short-term depression of AMPA receptor (AMPAR)-mediated currents, but the underlying mechanisms and its function for visual integration are not known. Here we identify CKAMP44 as a crucial auxiliary subunit of AMPARs in dLGN relay neurons, where it increases AMPAR-mediated current amplitudes and modulates gating of AMPARs. Importantly, CKAMP44 is responsible for the distinctive short-term depression in retinogeniculate synapses by reducing the rate of recovery from desensitization of AMPARs. Genetic deletion of CKAMP44 strongly reduces synaptic short-term depression, which leads to increased spike probability of relay neurons when activated with high-frequency inputs from retinogeniculate synapses. Finally, in vivo recordings reveal augmented ON- and OFF-responses of dLGN neurons in CKAMP44 knockout (CKAMP44−/−) mice, demonstrating the importance of CKAMP44 for modulating synaptic short-term depression and visual input integration. The function of receptor desensitization in vivo is not well understood. Here, the authors show that deletion of CKAMP44, an AMPAR auxiliary protein that modulates desensitization of AMPAR currents, affects synaptic facilitation at retinogeniculate synapses and visually-evoked firing in awake mice.
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影响因子：
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作者：
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通讯作者：
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