Involvement of MCH-oxytocin neural relay within the hypothalamus in murine nursing behavior

Abstract

Multiple sequential actions, performed during parental behaviors, are essential elements of reproduction in mammalian species. We showed that neurons expressing melanin concentrating hormone (MCH) in the lateral hypothalamic area (LHA) are more active in rodents of both sexes when exhibiting parental nursing behavior. Genetic ablation of the LHA-MCH neurons impaired maternal nursing. The post-birth survival rate was lower in pups born to female mice with congenitally ablated MCH neurons under control of tet-off system, exhibiting reduced crouching behavior. Virgin female and male mice with ablated MCH neurons were less interested in pups and maternal care. Chemogenetic and optogenetic stimulation of LHA-MCH neurons induced parental nursing in virgin female and male mice. LHA-MCH GABAergic neurons project fibres to the paraventricular hypothalamic nucleus (PVN) neurons. Optogenetic stimulation of PVN induces nursing crouching behavior along with increasing plasma oxytocin levels. The hypothalamic MCH neural relays play important functional roles in parental nursing behavior in female and male mice.

Social Network Plasticity of Mice Parental Behavior

“…Disruption of the neural relay of the MCH–oxytocin signaling, as seen in the case of MCH knockout from embryonic development with the Tet-off system ( Kato et al, 2021 ), might alter the efficacy of oxytocin anxiolytic buffering, resulting in an infanticidal tendency in males. Ablating MCH neurons in MCH-tTA; TetO DTA bigenic +/+ virgin males make them more aggressive toward pups, whereas bigenic +/+ virgin females are apathetic toward pups, similar to +/+ bigenic mothers ( Kato et al, 2021 ).…”

“…Disruption of the neural relay of the MCH–oxytocin signaling, as seen in the case of MCH knockout from embryonic development with the Tet-off system ( Kato et al, 2021 ), might alter the efficacy of oxytocin anxiolytic buffering, resulting in an infanticidal tendency in males. Ablating MCH neurons in MCH-tTA; TetO DTA bigenic +/+ virgin males make them more aggressive toward pups, whereas bigenic +/+ virgin females are apathetic toward pups, similar to +/+ bigenic mothers ( Kato et al, 2021 ). The ablation of MCH neurons affects the body weight, which appears to be decreased in both sexes ( Kato et al, 2021 ), and this finding is consistent with the results of a previous report showing engagement in infanticide due to hyperactivity ( Kokkotou et al, 2005 ; Zhou et al, 2005 ; Chee et al, 2019 ).…”

“…Ablating MCH neurons in MCH-tTA; TetO DTA bigenic +/+ virgin males make them more aggressive toward pups, whereas bigenic +/+ virgin females are apathetic toward pups, similar to +/+ bigenic mothers ( Kato et al, 2021 ). The ablation of MCH neurons affects the body weight, which appears to be decreased in both sexes ( Kato et al, 2021 ), and this finding is consistent with the results of a previous report showing engagement in infanticide due to hyperactivity ( Kokkotou et al, 2005 ; Zhou et al, 2005 ; Chee et al, 2019 ). A study using Cre-dependent DTA systems reported that adults lacking approximately 70% of MCH-expressing neurons spent less time exhibiting maternal behavior, whereas no infanticide was observed in males ( Kato et al, 2021 ).…”

“…As such, MCH acts as a neuromodulator that integrates various physiological functions. Recent evidence revealed a neural relay of MCH with the neurotransmitter γ-aminobutyric acid (GABA) projecting to the paraventricular nucleus (PVN) oxytocin neurons ( Kato et al, 2021 ; Figures 1 , 2A,B ). In this case, no sex difference in maternal behavior was observed when they were both pharmacogenetically and optogenetically stimulated.…”

“…(C) Oxytocin levels in plasma samples by the stimulation of optogenetics in the PVN. Mean ± SEM t -test, * p < 0.05 [modified from Kato et al (2021) ].…”