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Lrfn2-Mutant Mice Display Suppressed Synaptic Plasticity and Inhibitory Synapse Development and Abnormal Social Communication and Startle Response

Authors
Li, YanKim, RyunheeCho, Yi SulSong, Woo SeokKim, DoyounKim, KyungdeokRoh, Junyeop DanielChung, ChangukPark, HanwoolYang, EstherKim, Soo-JeongKo, JaewonKim, HyunKim, Myoung-HwanBae, Yong-ChulKim, Eunjoon
Issue Date
27-6월-2018
Publisher
SOC NEUROSCIENCE
Keywords
excitatory synaptic function; GABAergic neurons; inhibitory synapses; Lrfn2; NMDA receptor; social communication
Citation
JOURNAL OF NEUROSCIENCE, v.38, no.26, pp.5872 - 5887
Indexed
SCIE
SCOPUS
Journal Title
JOURNAL OF NEUROSCIENCE
Volume
38
Number
26
Start Page
5872
End Page
5887
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/74893
DOI
10.1523/JNEUROSCI.3321-17.2018
ISSN
0270-6474
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, SALM1expression 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.
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