TY - JOUR
T1 - Lrfn2-mutant mice display suppressed synaptic plasticity and inhibitory synapse development and abnormal social communication and startle response
AU - Li, Yan
AU - Kim, Ryunhee
AU - Cho, Yi Sul
AU - Song, Woo Seok
AU - Kim, Doyoun
AU - Kim, Kyungdeok
AU - Roh, Junyeop Daniel
AU - Chung, Changuk
AU - Park, Hanwool
AU - Yang, Esther
AU - Kim, Soo Jeong
AU - Ko, Jaewon
AU - Kim, Hyun
AU - Kim, Myoung Hwan
AU - Bae, Yong Chul
AU - Kim, Eunjoon
N1 - Funding Information:
This work was supported by the National Research Foundation of Korea (Ministry of Science, ICT and Future Planning Grant NRF-2017M3C7A1048566 to H.K., NRF Global PhD Fellowship Program Grant NRF-2015H1A2A1033937 to R.K., Grant NRF-2017R1A5A2015391 to Y.C.B., Grant 2016R1A2B200682 to J.K., and Grant NRF-2017R1D1A1B03032935 to M.H.K) and the Institute for Basic Science (Grant IBS-R002-D1 to E.K.).
PY - 2018/6/27
Y1 - 2018/6/27
N2 - 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.
AB - 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.
KW - Excitatory synaptic function
KW - GABAergic neurons
KW - Inhibitory synapses
KW - Lrfn2
KW - NMDA receptor
KW - Social communication
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U2 - 10.1523/JNEUROSCI.3321-17.2018
DO - 10.1523/JNEUROSCI.3321-17.2018
M3 - Article
C2 - 29798891
AN - SCOPUS:85050885459
VL - 38
SP - 5872
EP - 5887
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 26
ER -