Language

English

Publication Date

3-23-2026

Journal

bioRxiv

DOI

10.64898/2026.03.20.713203

PMID

41929114

PMCID

PMC13042152

PubMedCentral® Posted Date

3-23-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Male parenting behavior is highly conserved and activated only after offspring are born. Here we show that the behavioral switch from infanticide in virgin male mice to caregiving in wild-type sires is associated with enhanced expression and activation of Transient receptor potential channel 5 (Trpc5) in estrogen receptor α (Esr1)-expressing neurons in the hypothalamic medial preoptic area (MPOA). While selective deletion of Trpc5 from Esr1MPOA neurons diminishes paternal behavior in sires, overexpression of Trpc5 in these neurons converts the otherwise infanticidal virgin males to exhibit care to pups. Mechanistically, Trpc5-dependent changes in neuronal excitability underlie fatherhood-associated Esr1MPOA neuron plasticity. Notably, Trpc5 overexpression also enhances escape behavior and elicits exploratory diving behavior, suggesting that these neurons control a broader adaptive parenting response in males. These findings establish a Trpc5-dependent MPOA neural signal as a critical regulator of paternal behavior.

Keywords

Paternal behavior, Diving behavior, Medial preoptic area, Estrogen receptor α, Trpc5

Published Open-Access

yes

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