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J Neurosci. 2014 Nov 19;34(47):15779-92. doi: 10.1523/JNEUROSCI.1141-14.2014.

Netrin-G/NGL complexes encode functional synaptic diversification.

Author information

Laboratory for Behavioral Genetics, RIKEN Brain Science Institute (BSI), Wako, Saitama, 351-0198, Japan.
IDINE, Departamento de Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La Mancha, 13071 Albacete, Spain.
Research Resource Center, RIKEN BSI, Wako, Saitama, 351-0198, Japan.
Division of Cerebral Structure, National Institute for Physiological Science, Okazaki 444-8787, Japan, and IST Austria, 3400 Klosterneuburg, Austria.
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute (BSI), Wako, Saitama, 351-0198, Japan,


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.


excitatory synapse; mice; netrin-G1; netrin-G2; pathway specificity; trans-synaptic adhesion molecule

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