The lateral habenula integrates age and experience to promote social transitions in developing rats
Dana Cobb-Lewis,
Anne George,
Shannon Hu,
Katherine Packard,
Mingyuan Song,
Isabellah Nikitah,
Oliver Nguyen-Lopez,
Emily Tesone,
Jhanay Rowden,
Julie Wang,
Maya Opendak
Affiliations
Dana Cobb-Lewis
Kennedy Krieger Institute, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Anne George
Kennedy Krieger Institute, Baltimore, MD 21205, USA
Shannon Hu
Kennedy Krieger Institute, Baltimore, MD 21205, USA
Katherine Packard
Kennedy Krieger Institute, Baltimore, MD 21205, USA
Mingyuan Song
Kennedy Krieger Institute, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Isabellah Nikitah
Kennedy Krieger Institute, Baltimore, MD 21205, USA
Oliver Nguyen-Lopez
Kennedy Krieger Institute, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Emily Tesone
Kennedy Krieger Institute, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Jhanay Rowden
Kennedy Krieger Institute, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Julie Wang
Kennedy Krieger Institute, Baltimore, MD 21205, USA
Maya Opendak
Kennedy Krieger Institute, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding author
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.
