Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice

作者：Morimura Naoko^*; Yasuda Hiroki; Yamaguchi Kazuhiko; Katayama Kei ichi; Hatayama Minoru; Tomioka Naoko H; Odagawa Maya; Kamiya Akiko; Iwayama Yoshimi; Maekawa Motoko; Nakamura Kazuhiko; Matsuzaki Hideo; Tsujii Masatsugu; Yamada Kazuyuki; Yoshikawa Takeo; Aruga Jun^*

来源：Nature Communications, 2017, 8(1): 15800.

DOI：10.1038/ncomms15800

Lrfn2/SALM1 is a PSD-95-interacting synapse adhesion molecule, and human LRFN2 is associated with learning disabilities. However its role in higher brain function and underlying mechanisms remain unknown. Here, we show that Lrfn2 knockout mice exhibit autism-like behavioural abnormalities, including social withdrawal, decreased vocal communications, increased stereotyped activities and prepulse inhibition deficits, together with enhanced learning and memory. In the hippocampus, the levels of synaptic PSD-95 and GluA1 are decreased. The synapses are structurally and functionally immature with spindle shaped spines, smaller postsynaptic densities, reduced AMPA/NMDA ratio, and enhanced LTP. In vitro experiments reveal that synaptic surface expression of AMPAR depends on the direct interaction between Lrfn2 and PSD-95. Furthermore, we detect functionally defective LRFN2 missense mutations in autism and schizophrenia patients. Together, these findings indicate that Lrfn2/LRFN2 serve as core components of excitatory synapse maturation and maintenance, and their dysfunction causes immature/silent synapses with pathophysiological state.

• 出版日期2017-6-12
• 单位RIKEN