A Missense Variant at the Nrxn3 Locus Enhances Empathy Fear in the Mouse

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Title
A Missense Variant at the Nrxn3 Locus Enhances Empathy Fear in the Mouse
Author(s)
Sehoon Keum; Arie Kim; Jae Jin Shin; Jong-Hyun Kim; Joomin Park; Hee-Sup Shin
Publication Date
2018-05
Journal
NEURON, v.98, no.3, pp.588 - 601
Publisher
CELL PRESS
Abstract
Empathy is crucial for our emotional experience and social interactions, and its abnormalities manifest in various psychiatric disorders. Observational fear is a useful behavioral paradigm for assessing affective empathy in rodents. However, specific genes that regulate observational fear remain unknown. Here we showed that 129S1/SvImJ mice carrying a unique missense variant in neurexin 3 (Nrxn3) exhibited a profound and selective enhancement in observational fear. Using the CRISPR/Cas9 system, the arginine-to-tryptophan (R498W) change in Nrxn3 was confirmed to be the causative variant. Selective deletion of Nrxn3 in somatostatin-expressing (SST+) interneurons in the anterior cingulate cortex (ACC) markedly increased observational fear and impaired inhibitory synaptic transmission from SST+ neurons. Concordantly, optogenetic manipulation revealed that SST+ neurons in the ACC bidirectionally controlled the degree of socially transmitted fear. Together, these results provide insights into the genetic basis of behavioral variability and the neurophysiological mechanism controlling empathy in mammalian brains ª 2018 Elsevier Inc.
URI
https://pr.ibs.re.kr/handle/8788114/4511
ISSN
0896-6273
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > Journal Papers (저널논문)
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