CKAMP44 controls synaptic function and strength of relay neurons during early development of the dorsal lateral geniculate nucleus. (17th July 2022)

• Record Type: Journal Article
• Authors: Hetsch, Florian; Wang, Danni; Chen, Xufeng; Zhang, Jiong; Aslam, Muhammad; Kegel, Marcel; Tonner, Henrik; Grus, Franz; von Engelhardt, Jakob
• Is Part Of: Journal of physiology. Volume 600:Number 15(2022)
• Page Start: 3549
• Page End: 3565
• Publication Date: 2022-07-17
• Subjects: AMPA receptor -- CKAMP44 -- dLGN -- shisa9; Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP283172
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Abstract: Relay neurons of the dorsal lateral geniculate nucleus (dLGN) receive inputs from retinal ganglion cells via retinogeniculate synapses. These connections undergo pruning in the first 2 weeks after eye opening. The remaining connections are strengthened several‐fold by the insertion of AMPA receptors (AMPARs) into weak or silent synapses. In this study, we found that the AMPAR auxiliary subunit CKAMP44 is required for receptor insertion and function of retinogeniculate synapses during development. Genetic deletion of CKAMP44 resulted in decreased synaptic strength and a higher number of silent synapses in young (P9–11) mice. Recovery from desensitisation of AMPARs was faster in CKAMP44 knockout (CKAMP44 –/– ) than in wild‐type mice. Moreover, loss of CKAMP44 increased the probability of inducing plateau potentials, which are known to be important for eye‐specific input segregation and retinogeniculate synapse maturation. The anatomy of relay neurons in the dLGN was changed in young CKAMP44 –/– mice showing a transient increase in dendritic branching that normalised during later development (P26–33). Interestingly, input segregation in young CKAMP44 –/– mice was not affected when compared to wild‐type mice. These results demonstrate that CKAMP44 promotes maturation and modulates function of retinogeniculate synapses during early development of the visual system without affecting input segregation. Key points: Expression of CKAMP44 starts early during development of the dorsal lateral geniculate nucleus (dLGN) and remains stable in relay neurons and interneurons. Genetic deletion of CKAMP44 decreases synaptic strength and increases silent synapse number in dLGN relay neurons; increases the rate of recovery from desensitisation of AMPA receptors in dLGN relay neurons; and reduces synaptic short‐term depression in retinogeniculate synapses. The probability of inducing plateau potentials is elevated in relay neurons of CKAMP44 –/– mice. Eye‐specific input segregation is unaffected in the dLGN of CKAMP44 –/– mice. Deletion of CKAMP44 mildly affects dendritic arborisation of relay neurons in the dLGN. Abstract : Abstract figure legend AMPA receptor auxiliary subunit CKAMP44 influences synaptic function in retinogeniculate synapses of young mice. CKAMP44 unsilences synapses by recruiting AMPA receptors to the synapse. Furthermore, genetic deletion of CKAMP44 reduces short‐term depression and increases the probability of eliciting L‐type Ca 2+ channel‐mediated plateau potentials.