CAPS2 Deficiency Impairs the Release of the Social Peptide Oxytocin, as Well as Oxytocin-Associated Social Behavior

Ca -dependent activator protein for secretion 2 (CAPS2) regulates dense-core vesicle (DCV) exocytosis to facilitate peptidergic and catecholaminergic transmitter release. CAPS2 deficiency in mice has mild neuronal effects but markedly impairs social behavior. Rare alterations also occur in autism sp...

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Bibliographic Details
Published in:The Journal of neuroscience 2021-05, Vol.41 (20), p.4524-4535
Main Authors: Fujima, Shuhei, Yamaga, Ryosuke, Minami, Haruka, Mizuno, Shota, Shinoda, Yo, Sadakata, Tetsushi, Abe, Manabu, Sakimura, Kenji, Sano, Yoshitake, Furuichi, Teiichi
Format: Article
Language:English
Subjects:
Autism
Calcium
Calcium ions
Exocytosis
Hypothalamus
Neurotransmitter release
Oxytocin
Peptides
Pituitary
Social behavior
Social factors
Social interaction
Social interactions
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Summary:Ca -dependent activator protein for secretion 2 (CAPS2) regulates dense-core vesicle (DCV) exocytosis to facilitate peptidergic and catecholaminergic transmitter release. CAPS2 deficiency in mice has mild neuronal effects but markedly impairs social behavior. Rare alterations also occur in autism spectrum disorder, although whether CAPS2-mediated release influences social behavior remains unclear. Here, we demonstrate that CAPS2 is associated with DCV exocytosis-mediated release of the social interaction modulatory peptide oxytocin (OXT). CAPS2 is expressed in hypothalamic OXT neurons and localizes to OXT nerve projection and OXT release sites, such as the pituitary. KO mice exhibited reduced plasma albeit increased hypothalamic and pituitary OXT levels, indicating insufficient release. OXT neuron-specific conditional KO supported CAPS2 function in pituitary OXT release, also affording impaired social interaction and recognition behavior that could be ameliorated by exogenous OXT administered intranasally. Thus, CAPS2 appears critical for OXT release, thereby being associated with social behavior. The role of the neuropeptide oxytocin in enhancing social interaction and social bonding behavior has attracted considerable public and neuroscientific attention. A central issue in oxytocin biology concerns how oxytocin release is regulated. Our study provides an important insight into the understanding of oxytocin-dependent social behavior from the perspective of the CAPS2-regulated release mechanism.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.3240-20.2021