Kennedy Krieger Institute, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kennedy Krieger Institute, Baltimore, MD 21205, USA.
Cell Rep. 2024 Aug 27;43(8):114556. doi: 10.1016/j.celrep.2024.114556. Epub 2024 Aug 1.
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.
早期养育逆境(ECA)与社会行为缺陷和随后的精神病理学发展有关。然而,ECA 的婴儿神经基质还知之甚少。外侧缰核(LHb)是一个高度保守的大脑区域,与成人精神病理学有一致的联系,在大脑最容易受到环境影响的发育时期,对其研究还很不足。在这里,我们描述了 LHb 的结构和功能发育及其在婴儿和幼年大鼠幼仔中的行为作用。我们表明,LHb 促进了典型饲养的婴儿成熟时在威胁下的社会趋近行为的发展转变。相比之下,我们表明 ECA 破坏了缰核的发育,包括体积、蛋白表达、放电特性和皮质缰核连接。此外,抑制特定的皮质缰核投射可挽救 ECA 后婴儿的社会趋近缺陷。总之,这些结果确定了 LHb 中 ECA 的即时生物标志物,并强调了该区域作为早期社会处理和行为控制的部位。