Lrfn2-mutant mice display suppressed synaptic plasticity and inhibitory synapse development and abnormal social communication and startle response

Yan Li, Ryunhee Kim, Yi Sul Cho, Woo Seok Song, Doyoun Kim, Kyungdeok Kim, Junyeop Daniel Roh, Changuk Chung, Hanwool Park, Esther Yang, Soo Jeong Kim, Jaewon Ko, Hyun Kim, Myoung Hwan Kim, Yong Chul Bae, Eunjoon Kim

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

SALM1 (SALM (synaptic adhesion-like molecule), also known as LRFN2 (leucine rich repeat and fibronectin type III domain containing), is a postsynaptic density (PSD)-95-interacting synaptic adhesion molecule implicated in the regulation of NMDA receptor (NMDAR) clustering largely based on in vitro data, although its in vivo functions remain unclear. Here, we found that mice lacking SALM1/LRFN2 (Lrfn2-/- mice) show a normal density of excitatory synapses but altered excitatory synaptic function, including enhanced NMDAR-dependent synaptic transmission but suppressed NMDAR-dependent synaptic plasticity in the hippocampal CA1 region. Unexpectedly, SALM1 expression was detected in both glutamatergic and GABAergic neurons and Lrfn2-/- CA1 pyramidal neurons showed decreases in the density of inhibitory synapses and the frequency of spontaneous inhibitory synaptic transmission. Behaviorally, ultrasonic vocalization was suppressed in Lrfn2-/- pups separated from their mothers and acoustic startle was enhanced, but locomotion, anxiety-like behavior, social interaction, repetitive behaviors, and learning and memory were largely normal in adult male Lrfn2-/- mice. These results suggest that SALM1/LRFN2 regulates excitatory synapse function, inhibitory synapse development, and social communication and startle behaviors in mice.

Original languageEnglish
Pages (from-to)5872-5887
Number of pages16
JournalJournal of Neuroscience
Volume38
Issue number26
DOIs
Publication statusPublished - 2018 Jun 27

Keywords

  • Excitatory synaptic function
  • GABAergic neurons
  • Inhibitory synapses
  • Lrfn2
  • NMDA receptor
  • Social communication

ASJC Scopus subject areas

  • Neuroscience(all)

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