CKAMP44 modulates integration of visual inputs in the lateral geniculate nucleus

Xufeng Chen,Muhammad Aslam,Jakob Von Engelhardt,Kevin Allen,Tim Gollisch

doi:10.1038/s41467-017-02415-1

Abstract

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.

Highlights

Relay neurons in the dorsal lateral geniculate nucleus receive excitatory inputs from retinal ganglion cells (RGCs)
The AMPA/NMDA ratio was significantly reduced in both synapses of CKAMP44−/− mice (Fig. 1c, d and Supplementary Table 1), indicating that deletion of CKAMP44 reduces the number of AMPA receptor (AMPAR) in retinogeniculate and corticogeniculate synapses
Using wildtype and CKAMP44−/− mice, we showed that this auxiliary subunit increases AMPAR-mediated current amplitudes and modulates gating of AMPARs

Summary

Introduction

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. Gating kinetics of AMPARs in dLGN neurons, in particular the very slow recovery from desensitization, are very different from that of heterologously expressed tetrameric receptors[11]. This suggests that auxiliary subunits influence AMPAR function in dLGN neurons. The prototypical auxiliary subunit stargazin influences AMPARmediated currents in dLGN relay neurons[19] It renders recovery from desensitization faster[12], suggesting that another auxiliary subunit is responsible for the unusual AMPAR gating kinetics in dLGN relay neurons. Show that GSG1L and CKAMP39 are not highly expressed in in the thalamic region[18,21], suggesting that CKAMP44 may influence AMPAR function in this brain region

Methods

Results

Conclusion