Calcitonin receptor signaling in the medial preoptic area enables risk-taking maternal care

Chihiro Yoshihara; Kenichi Tokita; Teppo Maruyama; Misato Kaneko; Yousuke Tsuneoka; Kansai Fukumitsu; Eri Miyazawa; Kazutaka Shinozuka; Arthur J Huang; Katsuhiko Nishimori; Thomas J McHugh; Minoru Tanaka; Shigeyoshi Itohara; Kazushige Touhara; Kazunari Miyamichi; Kumi O Kuroda

doi:10.1016/j.celrep.2021.109204

Calcitonin receptor signaling in the medial preoptic area enables risk-taking maternal care

Cell Rep. 2021 Jun 1;35(9):109204. doi: 10.1016/j.celrep.2021.109204.

Authors

Chihiro Yoshihara¹, Kenichi Tokita², Teppo Maruyama³, Misato Kaneko³, Yousuke Tsuneoka⁴, Kansai Fukumitsu¹, Eri Miyazawa¹, Kazutaka Shinozuka¹, Arthur J Huang⁵, Katsuhiko Nishimori⁶, Thomas J McHugh⁵, Minoru Tanaka⁷, Shigeyoshi Itohara⁸, Kazushige Touhara⁹, Kazunari Miyamichi¹⁰, Kumi O Kuroda¹¹

Affiliations

¹ Laboratory for Affiliative Social Behavior, RIKEN Center for Brain Science, Saitama 351-0198, Japan.
² Laboratory for Affiliative Social Behavior, RIKEN Center for Brain Science, Saitama 351-0198, Japan; The Institute of Natural Sciences, Senshu University, Tokyo 101-8425, Japan.
³ Laboratory for Affiliative Social Behavior, RIKEN Center for Brain Science, Saitama 351-0198, Japan; Department of Animal Science, Faculty of Applied Life Science, Nippon Veterinary and Life Science University, Musashino, Tokyo 180-8602, Japan.
⁴ Laboratory for Affiliative Social Behavior, RIKEN Center for Brain Science, Saitama 351-0198, Japan; Department of Anatomy, Faculty of Medicine, Toho University, Tokyo 143-8540, Japan.
⁵ Laboratory for Circuit and Behavioral Physiology, RIKEN Center for Brain Science, Saitama 351-0198, Japan.
⁶ Department of Obesity and Internal Inflammation, Fukushima Medical University, Fukushima 960-1295, Japan.
⁷ Department of Animal Science, Faculty of Applied Life Science, Nippon Veterinary and Life Science University, Musashino, Tokyo 180-8602, Japan.
⁸ Laboratory for Behavioral Genetics, RIKEN Center for Brain Science, Saitama 351-0198, Japan.
⁹ Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; ERATO Touhara Chemosensory Signal Project, Japan Science and Technology Agency, The University of Tokyo, Tokyo 113-8657, Japan; International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo Institutes for Advanced Study, Tokyo 113-0033, Japan.
¹⁰ Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo Institutes for Advanced Study, Tokyo 113-0033, Japan; Laboratory for Comparative Connectomics, RIKEN Center for Biosystems Dynamics Research, Hyogo 650-0047, Japan.
¹¹ Laboratory for Affiliative Social Behavior, RIKEN Center for Brain Science, Saitama 351-0198, Japan. Electronic address: oyako.cbs@riken.jp.

PMID: 34077719
DOI: 10.1016/j.celrep.2021.109204

Abstract

Maternal mammals exhibit heightened motivation to care for offspring, but the underlying neuromolecular mechanisms have yet to be clarified. Here, we report that the calcitonin receptor (Calcr) and its ligand amylin are expressed in distinct neuronal populations in the medial preoptic area (MPOA) and are upregulated in mothers. Calcr+ MPOA neurons activated by parental care project to somatomotor and monoaminergic brainstem nuclei. Retrograde monosynaptic tracing reveals that significant modification of afferents to Calcr+ neurons occurs in mothers. Knockdown of either Calcr or amylin gene expression hampers risk-taking maternal care, and specific silencing of Calcr+ MPOA neurons inhibits nurturing behaviors, while pharmacogenetic activation prevents infanticide in virgin males. These data indicate that Calcr+ MPOA neurons are required for both maternal and allomaternal nurturing behaviors and that upregulation of amylin-Calcr signaling in the MPOA at least partially mediates risk-taking maternal care, possibly via modified connectomics of Calcr+ neurons postpartum.

Keywords: Iapp; Mus musculus; amylin; cMPOA; calcitonin receptor; central part of the medial preoptic area; infanticide; islet amyloid poly-peptide; maternal behavior; nurturing behavior; parental behavior.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Behavior, Animal / physiology*
Estrogens / metabolism
Female
Gene Silencing
Gene Targeting
Islet Amyloid Polypeptide / metabolism
Lactation
Ligands
Male
Maternal Behavior / physiology*
Mice
Mice, Inbred C57BL
Neurons / metabolism
Postpartum Period
Preoptic Area / metabolism*
Prolactin / metabolism
Receptors, Calcitonin / metabolism*
Risk-Taking*
Signal Transduction*
Synapses / metabolism
Up-Regulation

Substances

Estrogens
Islet Amyloid Polypeptide
Ligands
Receptors, Calcitonin
Prolactin