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.

中文翻译：

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CKAMP44调节视觉输入在外侧膝状核中的整合。

背外侧膝状核（dLGN）中的中继神经元从视网膜神经节细胞（RGC）接收兴奋性输入。维甲酸突触的特征是AMPA受体（AMPAR）介导的电流明显短期下降，但其潜在的机制及其视觉整合的功能尚不清楚。在这里，我们将CKAMP44识别为dLGN中继神经元中AMPAR的关键辅助亚基，它会增加AMPAR介导的电流幅度并调节AMPAR的门控。重要的是，CKAMP44通过降低AMPAR脱敏的恢复速率，导致视网膜新生突触的独特短期抑制。CKAMP44的基因缺失强烈降低了突触的短期抑郁，当通过视黄醛酸突触的高频输入激活时，这会导致中继神经元的尖峰概率增加。最后，体内记录显示CKAMP44敲除（CKAMP44^-/-）小鼠，证明CKAMP44在调节突触短期抑制和视觉输入整合中的重要性。