Sex-specific hypothalamic neural projection activity drives caregiving in mice

Abstract Infant care is critical for survival and healthy development. In laboratory mice, unmated males and females display infant-directed behavior ranging from neglect and aggression to alloparental care. Previous research suggests that excitatory neurons in the perifornical area of the hypothala...

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Main Authors: Ilaria Carta, Tushar Arora, Stefano Lutzu, Giovanni Podda, Gaspar Nicolay Vera Ortega, Stephanie Rudolph, Anita E. Autry
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59352-7
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author Ilaria Carta
Tushar Arora
Stefano Lutzu
Giovanni Podda
Gaspar Nicolay Vera Ortega
Stephanie Rudolph
Anita E. Autry
author_facet Ilaria Carta
Tushar Arora
Stefano Lutzu
Giovanni Podda
Gaspar Nicolay Vera Ortega
Stephanie Rudolph
Anita E. Autry
author_sort Ilaria Carta
collection DOAJ
description Abstract Infant care is critical for survival and healthy development. In laboratory mice, unmated males and females display infant-directed behavior ranging from neglect and aggression to alloparental care. Previous research suggests that excitatory neurons in the perifornical area of the hypothalamus (PeFA) mediate pup-directed aggression. Because medial preoptic area galanin-expressing (MPOAGal) neurons are indispensable for caregiving, we hypothesized that inhibitory MPOAGal projections to PeFA prevent pup-directed aggression. We found that MPOAGal→PeFA projection activity increased during pup approach in both sexes, and alloparental females showed increased projection activity during pup grooming compared to males. Anatomical differences did not explain this disparity in activity between sexes. Optogenetic inhibition of MPOAGal→PeFA projections reduced pup grooming in alloparental females but did not affect male caregiving, while projection stimulation reduced infant-directed aggression in males. Altogether, we show that this projection holds greater significance for female caregiving due to its heightened activity during natural behavior toward pups.
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spelling doaj-art-3bb3e123ec5340df916a6bd3644ceb242025-08-20T01:47:29ZengNature PortfolioNature Communications2041-17232025-05-0116111510.1038/s41467-025-59352-7Sex-specific hypothalamic neural projection activity drives caregiving in miceIlaria Carta0Tushar Arora1Stefano Lutzu2Giovanni Podda3Gaspar Nicolay Vera Ortega4Stephanie Rudolph5Anita E. Autry6Dominick P. Purpura Department of Neuroscience, Albert Einstein College of MedicineDominick P. Purpura Department of Neuroscience, Albert Einstein College of MedicineDominick P. Purpura Department of Neuroscience, Albert Einstein College of MedicineDominick P. Purpura Department of Neuroscience, Albert Einstein College of MedicineDominick P. Purpura Department of Neuroscience, Albert Einstein College of MedicineDominick P. Purpura Department of Neuroscience, Albert Einstein College of MedicineDominick P. Purpura Department of Neuroscience, Albert Einstein College of MedicineAbstract Infant care is critical for survival and healthy development. In laboratory mice, unmated males and females display infant-directed behavior ranging from neglect and aggression to alloparental care. Previous research suggests that excitatory neurons in the perifornical area of the hypothalamus (PeFA) mediate pup-directed aggression. Because medial preoptic area galanin-expressing (MPOAGal) neurons are indispensable for caregiving, we hypothesized that inhibitory MPOAGal projections to PeFA prevent pup-directed aggression. We found that MPOAGal→PeFA projection activity increased during pup approach in both sexes, and alloparental females showed increased projection activity during pup grooming compared to males. Anatomical differences did not explain this disparity in activity between sexes. Optogenetic inhibition of MPOAGal→PeFA projections reduced pup grooming in alloparental females but did not affect male caregiving, while projection stimulation reduced infant-directed aggression in males. Altogether, we show that this projection holds greater significance for female caregiving due to its heightened activity during natural behavior toward pups.https://doi.org/10.1038/s41467-025-59352-7
spellingShingle Ilaria Carta
Tushar Arora
Stefano Lutzu
Giovanni Podda
Gaspar Nicolay Vera Ortega
Stephanie Rudolph
Anita E. Autry
Sex-specific hypothalamic neural projection activity drives caregiving in mice
Nature Communications
title Sex-specific hypothalamic neural projection activity drives caregiving in mice
title_full Sex-specific hypothalamic neural projection activity drives caregiving in mice
title_fullStr Sex-specific hypothalamic neural projection activity drives caregiving in mice
title_full_unstemmed Sex-specific hypothalamic neural projection activity drives caregiving in mice
title_short Sex-specific hypothalamic neural projection activity drives caregiving in mice
title_sort sex specific hypothalamic neural projection activity drives caregiving in mice
url https://doi.org/10.1038/s41467-025-59352-7
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