Synaptic cell adhesion molecules are increasingly gaining attention for conferring specific properties to individual synapses. Netrin-G1 and netrin-G2 are trans-synaptic adhesion molecules that distribute on distinct axons, and their presence restricts the expression of their cognate receptors, NGL1 and NGL2, respectively, to specific subdendritic segments of target neurons. However, the neural circuits and functional roles of netrin-G isoform complexes remain unclear. Here, we use netrin-G-KO and NGL-KO mice to reveal that netrin-G1/NGL1 and netrin-G2/NGL2 interactions specify excitatory synapses in independent hippocampal pathways. In the hippocampal CA1 area, netrin-G1/NGL1 and netrin-G2/NGL2 were expressed in the temporoammonic and Schaffer collateral pathways, respectively. The lack of presynaptic netrin-Gs led to the dispersion of NGLs from postsynaptic membranes. In accord, netrin-G mutant synapses displayed opposing phenotypes in long-term and short-term plasticity through discrete biochemical pathways. The plasticity phenotypes in netrin-G-KOs were phenocopied in NGL-KOs, with a corresponding loss of netrin-Gs from presynaptic membranes. Our findings show that netrin-G/NGL interactions differentially control synaptic plasticity in distinct circuits via retrograde signaling mechanisms and explain how synaptic inputs are diversified to control neuronal activity.
Journal of Neuroscience
This work was supported by “Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)” initiated by the Council for Science and Technology Policy.
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Matsukawa H, Akiyoshi Nishimura S, Zhang Q, et al. Netrin-G/NGL complexes encode functional synaptic diversification. Journal of Neuroscience. 2014;34(47):15779-15792. doi:10.1523/JNEUROSCI.1141-14.2014
Matsukawa, H., Akiyoshi Nishimura, S., Zhang, Q., Luján, R., Yamaguchi, K., Goto, H., … Itohara, S. (2014). Netrin-G/NGL complexes encode functional synaptic diversification. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1141-14.2014
Matsukawa, Hiroshi, Sachiko Akiyoshi Nishimura, Qi Zhang, Rafael Luján, Kazuhiko Yamaguchi, Hiromichi Goto, Kunio Yaguchi, et al. “Netrin-G/NGL Complexes Encode Functional Synaptic Diversification.” Journal of Neuroscience. Society for Neuroscience, 2014. https://doi.org/10.1523/JNEUROSCI.1141-14.2014.
H. Matsukawa et al., “Netrin-G/NGL complexes encode functional synaptic diversification,” Journal of Neuroscience, vol. 34, no. 47. Society for Neuroscience, pp. 15779–15792, 2014.
Matsukawa H, Akiyoshi Nishimura S, Zhang Q, Luján R, Yamaguchi K, Goto H, Yaguchi K, Hashikawa T, Sano C, Shigemoto R, Nakashiba T, Itohara S. 2014. Netrin-G/NGL complexes encode functional synaptic diversification. Journal of Neuroscience. 34(47), 15779–15792.
Matsukawa, Hiroshi, et al. “Netrin-G/NGL Complexes Encode Functional Synaptic Diversification.” Journal of Neuroscience, vol. 34, no. 47, Society for Neuroscience, 2014, pp. 15779–92, doi:10.1523/JNEUROSCI.1141-14.2014.