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The lateral habenula integrates age and experience to promote social transitions in developing rats

Early caregiving adversity (ECA) is associated with social behavior deficits and later development of psychopathology. However, the infant neural substrates of ECA are poorly understood. The lateral habenula (LHb), a highly conserved brain region with consistent links to adult psychopathology, is un...

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Bibliographic Details
Published in:Cell reports (Cambridge) 2024-08, Vol.43 (8), p.114556-114556, Article 114556
Main Authors: Cobb-Lewis, Dana, George, Anne, Hu, Shannon, Packard, Katherine, Song, Mingyuan, Nikitah, Isabellah, Nguyen-Lopez, Oliver, Tesone, Emily, Rowden, Jhanay, Wang, Julie, Opendak, Maya
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Language:English
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Summary:Early caregiving adversity (ECA) is associated with social behavior deficits and later development of psychopathology. However, the infant neural substrates of ECA are poorly understood. The lateral habenula (LHb), a highly conserved brain region with consistent links to adult psychopathology, is understudied in development, when the brain is most vulnerable to environmental impacts. Here, we describe the structural and functional ontogeny of the LHb and its behavioral role in infant and juvenile rat pups. We show that the LHb promotes a developmental transition in social approach behavior under threat as typically reared infants mature. By contrast, we show that ECA disrupts habenular ontogeny, including volume, protein expression, firing properties, and corticohabenular connectivity. Furthermore, inhibiting a specific corticohabenular projection rescues infant social approach deficits following ECA. Together, these results identify immediate biomarkers of ECA in the LHb and highlight this region as a site of early social processing and behavior control. [Display omitted] •LHb plays distinct roles in infant and juvenile rat social approach behaviors•Early adversity disrupts LHb structural and functional growth curves•A specific mPFC-LHb circuit drives infant social deficits after adversity Cobb-Lewis et al. demonstrate that the LHb plays distinct roles in infant and juvenile rat social approach behaviors. Early adversity disrupts LHb structural and functional growth curves, including volume, protein expression, and firing properties. Finally, inhibiting a specific corticohabenular projection rescues social deficits in adversity-reared pups.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2024.114556