Neuronal Ensembles Formed by Early-Life Stress Mediate Lifelong Stress Hypersensitivity
Julie-Anne Balouek, Christabel A. Mclain, Adelaide R. Minerva, Rabekah L. Rashford, Shannon N. Bennett, Forrest D. Rogers, and Catherine Jensen Peña
(see pages 5996–6009)
When people experience early-life stress (ELS), it sensitizes them to later instances of stress, which can ultimately lead to anxiety and depression. But as prevalent as various forms of ELS are, the mechanisms through which stress sensitization occurs are unknown. In this issue, Balouek and colleagues investigated whether ELS forms neuronal ensembles that are more easily activated by adult stress. They used a transgenic mouse line enabling them to genetically tag and track experience-activated neurons and found that ELS-activated neurons in the NAc were preferentially reactivated by adult stress. They next tested whether reactivation of ELS-activated ensembles is necessary for stress hypersensitivity. They expressed a chemogenetic receptor in control or ELS-activated neurons of mouse pups to inhibit these neurons while mice experienced stress in adulthood. Inhibiting ELS-activated neuron ensembles, but not control tagged neurons, during adult stress ameliorated sensitivity to the development of depression-like symptoms. These findings demonstrate that ELS-induced stress hypersensitivity may be encoded by NAc neuronal ensembles. The implications of this work are considerable: it may inform novel treatment strategies for those who experience ELS and are at higher risk for developing anxiety and depression.
Each panel contains representative 20× images of the NAc of mice from four groups (Std-Ctrl, ELS-Ctrl, Std-CNSDS, or ELS-CNSDS). Scale bar, 50 μm. Arrows indicate colocalized GFP+ (ELS-activated) and cFos+ (CNSDS-activated) cells.
Development of Cortical Spatial Mapping
Ying Huang, Zhengwang Wu, Tengfei Li, Xifeng Wang, Ya Wang, Lei Xing, Hongtu Zhu, Weili Lin, Li Wang, Lei Guo, John H. Gilmore, and Gang Li
(see pages 6010–6020)
The cerebral cortex is the outermost layer of the brain and consists of nearly half its total weight. This critical brain mass is associated with “higher order processes,” such as consciousness, emotion, reasoning, language, and memory. Neuroimaging studies have identified cortical thickness (CT) and surface area (SA) as key morphological features of the cortex that impact its functioning. These studies have demonstrated that CT and SA growth between the ages of 1 and 11 years is critical for proper cortical functioning in adulthood, but genetic predisposition to CT and SA abnormalities in development, which may evolve throughout the lifespan into adulthood, is unexplored. In this issue, Huang and colleagues imaged neonatal twin brains to reveal parcellation maps of CT and SA, or groupings of specific cortical regions driven by distinct genetic information. This experimental strategy and finding are completely unprecedented. The investigators next further explored the implications of this finding. They compared genetic parcellations in neonates with those in adults to discover that some genetic regions bear similarity, especially the SA in the medial surface, but most are different. These findings provide critical insights into the genetically regulated spatial mapping of the cerebral cortex early in development and the significant changes these maps undergo by adulthood.
Footnotes
This Week in The Journal was written by Paige McKeon
