鹿児島大学 博士(医学) Doctor of Philosophy in Medical Science 博士論文全文, 博士論文要旨 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/NGL1and netrin-G2/NGL2 interactions specify excitatory synapses in independent hippocampal pathways. In the hippocampalCA1area, 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. Hiroshi Matsukawa, Sachiko Akiyoshi-Nishimura, Qi Zhang, Rafael Luján, Kazuhiko Yamaguchi, Hiromichi Goto, Kunio Yaguchi, Tsutomu Hashikawa, Chie Sano, Ryuichi Shigemoto, Toshiaki Nakashiba and Shigeyoshi Itohara Netrin-G/NGL Complexes Encode Functional Synaptic Diversification Journal of Neuroscience 2014, 34 (47) p.15779-15792 DOI: https://doi.org/10.1523/JNEUROSCI.1141-14.2014 doctoral thesis