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

外侧缰核整合年龄和经验,促进大鼠发育过程中的社会转变

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作者:Dana Cobb-Lewis, Anne George, Shannon Hu, Katherine Packard, Mingyuan Song, Isabellah Nikitah, Oliver Nguyen-Lopez, Emily Tesone, Jhanay Rowden, Julie Wang, Maya Opendak

Abstract

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.

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