Journal Article DZNE-2020-06058

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CKAMP44 modulates integration of visual inputs in the lateral geniculate nucleus.

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2018
Nature Publishing Group UK [London]

Nature Communications 9(1), 261 () [10.1038/s41467-017-02415-1]

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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.

Keyword(s): Animals (MeSH) ; Electroretinography (MeSH) ; Excitatory Postsynaptic Potentials: physiology (MeSH) ; Female (MeSH) ; Geniculate Bodies: cytology (MeSH) ; Geniculate Bodies: metabolism (MeSH) ; Geniculate Bodies: physiology (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Nerve Tissue Proteins: genetics (MeSH) ; Nerve Tissue Proteins: metabolism (MeSH) ; Neurons: metabolism (MeSH) ; Neurons: physiology (MeSH) ; Photic Stimulation (MeSH) ; Receptors, AMPA: metabolism (MeSH) ; Retina: cytology (MeSH) ; Retina: metabolism (MeSH) ; Retina: physiology (MeSH) ; Synapses: physiology (MeSH) ; Synaptic Transmission: genetics (MeSH) ; Synaptic Transmission: physiology (MeSH) ; CKAMP44 protein, mouse ; Nerve Tissue Proteins ; Receptors, AMPA

Classification:

Contributing Institute(s):
  1. Synaptic Signalling and Neurodegeneration (AG Engelhardt)
Research Program(s):
  1. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2018
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Medline ; Creative Commons Attribution CC BY (No Version) ; DOAJ ; OpenAccess ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; IF >= 15 ; JCR ; SCOPUS ; Web of Science Core Collection ; Zoological Record
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 Record created 2020-02-18, last modified 2024-05-11


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