ArticleProceedings of the National Academy of Sciences of the United States of America2023
Anterior cingulate cortex orexin signaling mediates early-life stress-induced social impairment in females.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- A Meta-Analysis of the Effects of Early Life Stress on the Prefrontal Cortex Transcriptome Reveals Long-Term Downregulation of Myelin-Related Gene Expression.Brain and behavior · 2025Pooled it
- Functional Plasticity of Orexin/Hypocretin Neurons Balances Stress States.Biological psychiatry · 2026Review
- Empathy and prosocial behavior powered by orexin-driven theta oscillations.Science (New York, N.Y.) · 2026Article
- Orexinergic regulation of GABAergic input onto pyramidal neurons in the anterior cingulate cortex.Biophysical journal · 2025Article
- Hippocampal area CA2 activity supports social investigation following an acute social stress.Molecular psychiatry · 2025Article
- Structural basis for the inhibition of cystathionine-β-synthase by isoflurane and its role in anaesthesia-induced social dysfunction in mice.British journal of anaesthesia · 2025Article
- Social context restructures behavioral syntax in mice.Frontiers in behavioral neuroscience · 2025Article
- Development of the rodent prefrontal cortex: circuit formation, plasticity, and impacts of early life stress.Frontiers in neural circuits · 2025Review
- Orexins/Hypocretins: Gatekeepers of Social Interaction and Motivation.International journal of molecular sciences · 2024Review
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Early-life stress has long-term impacts on the structure and function of the anterior cingulate cortex (ACC), and raises the risk of adult neuropsychiatric disorders including social dysfunction. The underlying neural mechanisms, however, are still uncertain. Here, we show that, in female mice, maternal separation (MS) during the first three postnatal weeks results in social impairment accompanied with hypoactivity in pyramidal neurons (PNs) of the ACC. Activation of ACC PNs ameliorates MS-induced social impairment. Neuropeptide Hcrt, which encodes hypocretin (orexin), is the top down-regulated gene in the ACC of MS females. Activating ACC orexin terminals enhances the activity of ACC PNs and rescues the diminished sociability observed in MS females via an orexin receptor 2 (OxR2)-dependent mechanism. Our results suggest orexin signaling in the ACC is critical in mediating early-life stress-induced social impairment in females.
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