Effects of MEK1/2 blocker U0126 on the medial preoptic synapse and behavioral selection of male mice

The central part of the mouse medial preoptic area (cMPOA) is involved in parental behavior because the neurotoxic lesion of the cMPOA disturbed parental behavior and switched to infanticidal behavior. The cMPOA receives projection from many brain regions, including the medial amygdala (Me). We have...

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Main Authors: Yumi Hamasaki, Masabumi Minami, Taiju Amano
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Neuroscience Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0168010225001129
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author Yumi Hamasaki
Masabumi Minami
Taiju Amano
author_facet Yumi Hamasaki
Masabumi Minami
Taiju Amano
author_sort Yumi Hamasaki
collection DOAJ
description The central part of the mouse medial preoptic area (cMPOA) is involved in parental behavior because the neurotoxic lesion of the cMPOA disturbed parental behavior and switched to infanticidal behavior. The cMPOA receives projection from many brain regions, including the medial amygdala (Me). We have previously found that optogenetic inhibition of the projection pathway from the Me to the cMPOA in virgin male mice suppressed the infanticidal behavior of virgin mice toward pups. Furthermore, electrophysiological analysis has revealed that intracellular signaling-mediated disinhibition occurs in the cMPOA neurons during the transition from virgin to father in gestation experience (FGE) mice. However, the specific downstream signal transduction pathway remains unclear. In this study, we utilized U0126, a MEK1/2 inhibitor, because U0126 has been reported to modulate GABAergic currents. Therefore, we examined the contribution of U0126 at the synaptic and behavioral levels. Applying U0126 to the cMPOA neurons in FGE mice restored eIPSP as much as that in cMPOA neurons in virgin mice. Furthermore, microinfusion of U0126 into the cMPOA shifted the behavioral pattern of FGE mice toward infanticide. These changes were not observed in the mice that experienced parenting. The results suggest that MEK1/2 mediates neurotransmission in the cMPOA and contributes to the stage transition from virgin to FGE mice after mating with females.
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spelling doaj-art-d1efc5b3a3714c808323407883e894302025-08-20T03:36:52ZengElsevierNeuroscience Research0168-01022025-09-0121810492910.1016/j.neures.2025.104929Effects of MEK1/2 blocker U0126 on the medial preoptic synapse and behavioral selection of male miceYumi Hamasaki0Masabumi Minami1Taiju Amano2Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, JapanDepartment of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, JapanCorrespondence to: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.; Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, JapanThe central part of the mouse medial preoptic area (cMPOA) is involved in parental behavior because the neurotoxic lesion of the cMPOA disturbed parental behavior and switched to infanticidal behavior. The cMPOA receives projection from many brain regions, including the medial amygdala (Me). We have previously found that optogenetic inhibition of the projection pathway from the Me to the cMPOA in virgin male mice suppressed the infanticidal behavior of virgin mice toward pups. Furthermore, electrophysiological analysis has revealed that intracellular signaling-mediated disinhibition occurs in the cMPOA neurons during the transition from virgin to father in gestation experience (FGE) mice. However, the specific downstream signal transduction pathway remains unclear. In this study, we utilized U0126, a MEK1/2 inhibitor, because U0126 has been reported to modulate GABAergic currents. Therefore, we examined the contribution of U0126 at the synaptic and behavioral levels. Applying U0126 to the cMPOA neurons in FGE mice restored eIPSP as much as that in cMPOA neurons in virgin mice. Furthermore, microinfusion of U0126 into the cMPOA shifted the behavioral pattern of FGE mice toward infanticide. These changes were not observed in the mice that experienced parenting. The results suggest that MEK1/2 mediates neurotransmission in the cMPOA and contributes to the stage transition from virgin to FGE mice after mating with females.http://www.sciencedirect.com/science/article/pii/S0168010225001129Paternal behaviorInfanticideSynapseMEK1/2
spellingShingle Yumi Hamasaki
Masabumi Minami
Taiju Amano
Effects of MEK1/2 blocker U0126 on the medial preoptic synapse and behavioral selection of male mice
Neuroscience Research
Paternal behavior
Infanticide
Synapse
MEK1/2
title Effects of MEK1/2 blocker U0126 on the medial preoptic synapse and behavioral selection of male mice
title_full Effects of MEK1/2 blocker U0126 on the medial preoptic synapse and behavioral selection of male mice
title_fullStr Effects of MEK1/2 blocker U0126 on the medial preoptic synapse and behavioral selection of male mice
title_full_unstemmed Effects of MEK1/2 blocker U0126 on the medial preoptic synapse and behavioral selection of male mice
title_short Effects of MEK1/2 blocker U0126 on the medial preoptic synapse and behavioral selection of male mice
title_sort effects of mek1 2 blocker u0126 on the medial preoptic synapse and behavioral selection of male mice
topic Paternal behavior
Infanticide
Synapse
MEK1/2
url http://www.sciencedirect.com/science/article/pii/S0168010225001129
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AT taijuamano effectsofmek12blockeru0126onthemedialpreopticsynapseandbehavioralselectionofmalemice