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

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. [Display omitted] •Calcitonin receptor and its ligand amylin are expressed in the medial preoptic area•Calcitonin receptor + neurons are essential for maternal and alloparental care•Both calcitonin receptor and amylin are upregulated in postpartum mother mice•Calcitonin receptor upregulation takes part in risk-taking maternal behavior Yoshihara et al. demonstrate that calcitonin receptor (Calcr)-expressing neurons in the central part of the medial preoptic area (cMPOA) are indispensable for both maternal and alloparental care in mice and that Calcr and its ligand amylin mediate heightened maternal motivation to care for young even under risky conditions.