ArticleTranslational psychiatry2024
Lateral hypothalamus orexinergic projection to the medial prefrontal cortex modulates chronic stress-induced anhedonia but not anxiety and despair.
Article in Translational psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Sex-Specific Hippocampal Phosphoproteomic Features Associated with Stress-Induced Phenotypes in Mice Exposed to Chronic Restraint Stress.Neurochemical research · 2026Article
- Stress, stress systems, and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Electroacupuncture alleviates depression and gastrointestinal dysfunction by rebalancing GABAergic activity in the central amygdala.World journal of psychiatry · 2026Article
- Implication of orexin transmission in chronic stress, hyperarousal, and neuroplasticity deficits: a mechanistic framework for depression and anxiety.Frontiers in psychiatry · 2026Review
- Maladaptive Neuroplasticity Under Stress: Insights into Neuronal and Synaptic Changes in the Prefrontal Cortex.Molecular neurobiology · 2025Review
- Disrupting the Gut-Brain Axis: How Artificial Sweeteners Rewire Microbiota and Reward Pathways.International journal of molecular sciences · 2025Review
- Mesoscale brain-wide fluctuation analysis: revealing ketamine's rapid antidepressant across multiple brain regions.Translational psychiatry · 2025Article
- Orexin mechanisms in the prelimbic cortex modulate the expression of contextual conditioned fear.Psychopharmacology · 2025Article
- Hypocretin: a promising target for the regulation of homeostasis.Frontiers in neuroscience · 2025Review
- Neuropeptidergic systems in psychiatric disorders.Frontiers in endocrinology · 2025Review
- Spatial mRNA expression patterns of orexin receptors in the dorsal hippocampus.Scientific reports · 2024Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic stress-induced anxiodepression is a common health problem, however its potential neurocircuitry mechanism remains unclear. We used behavioral, patch-clamp electrophysiology, chemogenetic, and optogenetic approaches to clarify the response of the lateral hypothalamus (LH) and the medial prefrontal cortex (mPFC) to stress, confirmed the structural connections between the LH and mPFC, and investigated the role of the LH-mPFC pathway in chronic stress-induced anxiodepression symptoms. Unpredictable chronic mild stress (UCMS) caused anxiodepression-like behaviors, including anxiety, anhedonia, and despair behaviors. We discovered that the activity of the LH and mPFC was both increased after restraint stress (RS), a stressor of UCMS. Then we found that the orexinergic neurons in the LH predominantly project to the glutamatergic neurons in the mPFC, and the excitability of these neurons were increased after UCMS. In addition, overactivated LH orexinergic terminals in the mPFC induced anhedonia but not anxiety and despair behaviors in naive mice. Moreover, chemogenetically inhibited LH-mPFC orexinergic projection neurons and blocked the orexin receptors in the mPFC alleviated anhedonia but not anxiety and despair behaviors in UCMS-treated mice. Our study identified a new neurocircuit from LH orexinergic neurons to mPFC and revealed its role in regulating anhedonia in response to stress. Overactivation of LH
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