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Researchers at the University of Tsukuba have identified neurons that are essential for mice to engage in social interactions with novel individuals. These neurons, which are located in the central nucleus of the amygdala, express a receptor called NPBWR1. Additionally, this study reveals that genetic polymorphisms in the human NPBWR1 gene influence social behavior when people interact with strangers.

Tsukuba, Japan—The ability to engage in new social interactions is vital for social animals. This behavior is often driven by a preference for interacting with novel individuals over familiar ones, which is known as "social novelty preference." This trait enhances the expansion of social networks but also carries potential risks. The molecular and neural mechanisms that balance these benefits and risks have remained poorly understood until now.

This study demonstrates that the activation of NPBWR1 neurons in the central nucleus of the amygdala is crucial for mice to engage in social interactions with novel individuals. Moreover, it shows that activating these neurons restores social behavior impaired by chronic social defeat stress, which is a psychological stress caused by territorial aggression among mice.

Our investigation reveals that the overexpression of the human NPBWR1 gene in mouse NPBWR1 neurons prevented the typical increase in the neuronal activity of NPBWR1 neurons that occurs when novel individuals are encountered and leads to reduced sociability. Interestingly, this effect is not observed when the human NPBWR1 gene carries a single nucleotide polymorphism (SNP), which suggests that variations in the NPBWR1 gene could affect sociability traits. These findings highlight the role of NPBWR1 neurons in regulating social novelty preference and suggest that polymorphisms of the human NPBWR1 gene could influence personality traits that are related to sociability.

These results also have significant implications for the discovery of drugs that target the human NPBWR1 receptor and offer potential new treatments for social disorders such as depression and autism spectrum disorder.

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This study was supported by a JSPS KAKENHI Grant-in-Aid for Scientific Research (B) (JP18H02595 to T.S. and JP21H02660 to S.S.), a KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas, "Willdynamics" (16H06401), JSPS KAKENHI grant number JP19K22465 (to T.S.) and 23H04661 (to S.S), JSPS Fund for the Promotion of Joint International Research grant number 22K21351 (to T.S.), JST CREST grant number JPMJCR1655 Japan (to T.S.), Japan Foundation for Applied Enzymology (to S.S), Naito Foundation (to S.S.), Senri Life Science Foundation (to S.S), Takeda Science Foundation (to S.S), Uehara Memorial Foundation (to S.S. and T.S.), Grant-in Scientific Research on Innovation Areas "Integrative Research towards Elucidation of Generative Brain Systems for Individuality" (19H04894) (to S.S.), and AMED grant number JP21zf0127005 (to T.S.).

Original Paper

Title of original paper:

Central Amygdala NPBWR1 Neurons Facilitate Social Novelty Seeking and New Social Interactions.

Journal:

Science Advances

DOI:

10.1126/sciadv.adn1335

Correspondence

Professor SAKURAI Takeshi
Institute of Medicine
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba

Related Link

Institute of Medicine

International Institute for Integrative Sleep Medicine (WPI-IIIS)