ArticleFrontiers in neuroscience2018
Orexin Depolarizes Central Amygdala Neurons via Orexin Receptor 1, Phospholipase C and Sodium-Calcium Exchanger and Modulates Conditioned Fear.
Article in Frontiers in neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Small molecule orexin agonist ROXA-47 enhances learning and memory in mice.Pharmacology, biochemistry, and behavior · 2026Article
- Functional Plasticity of Orexin/Hypocretin Neurons Balances Stress States.Biological psychiatry · 2026Review
- Neurobiological correlates of behavioral resilience to chronic alcohol and acute stress in male and female rats.Translational psychiatry · 2026Article
- Optogenetic Hedonic Hotspots in the Orbitofrontal Cortex and Insula: Causing Enhancement of Sweetness "Liking".The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Social defeat stress responses in the stress alternative model are dependent on sex and anterior basolateral amygdala orexin 2 receptors.Biology of sex differences · 2026Article
- Implication of orexin transmission in chronic stress, hyperarousal, and neuroplasticity deficits: a mechanistic framework for depression and anxiety.Frontiers in psychiatry · 2026Review
- Recording of Age-Related Changes on Murine and Human Brain Slices.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Identification of a novel perifornical-hypothalamic-area-projecting serotonergic system that inhibits innate panic and conditioned fear responses.Translational psychiatry · 2024Article
- The role of the orexin system in the neurobiology of anxiety disorders: Potential for a novel treatment target.Neuroscience applied · 2024Review
- Hypocretin role in posttraumatic stress disorder-like behaviors induced by a novel stress protocol in mice.Frontiers in psychiatry · 2023Article
- Amygdala neurocircuitry at the interface between emotional regulation and narcolepsy with cataplexy.Frontiers in neuroscience · 2023Review
- Hypothalamic orexins as possible therapeutic agents in threat and spatial memory disorders.Frontiers in behavioral neuroscience · 2023Review
- An interaction between basolateral amygdala orexinergic and endocannabinoid systems in inducing anti-nociception in the rat formalin test.Psychopharmacology · 2022Article
- Exploring the Therapeutic Potential of Targeting Purinergic and Orexinergic Receptors in Alcoholic Neuropathy.Neurotoxicity research · 2022Review
- Orexin/Hypocretin System Dysfunction in ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations).Neuropsychiatric disease and treatment · 2022Article
- Neuropeptide S Receptor Stimulation Excites Principal Neurons in Murine Basolateral Amygdala through a Calcium-Dependent Decrease in Membrane Potassium Conductance.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Orexin-A Intensifies Mouse Pupillary Light Response by Modulating Intrinsically Photosensitive Retinal Ganglion Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Genetic Up-Regulation or Pharmacological Activation of the NaMolecular neurobiology · 2020Article
- Orexin Receptor Antagonists as Emerging Treatments for Psychiatric Disorders.Neuroscience bulletin · 2020Review
- Exogenous Orexin-A Microinjected Into Central Nucleus of the Amygdala Modulates Feeding and Gastric Motility in Rats.Frontiers in neuroscience · 2020Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Orexins (OX), also known as hypocretins, are excitatory neuropeptides with well-described roles in regulation of wakefulness, arousal, energy homeostasis, and anxiety. An additional and recently recognized role of OX is modulation of fear responses. We studied the OX neurons of the perifornical hypothalamus (PeF) which send projections to the amygdala, a region critical in fear learning and fear expression. Within the amygdala, the highest density of OX-positive fibers was detected in the central nucleus (CeA). The specific mechanisms underlying OX neurotransmission within the CeA were explored utilizing rat brain slice electrophysiology, pharmacology, and chemogenetic stimulation. We show that OX induces postsynaptic depolarization of medial CeA neurons that is mediated by OX receptor 1 (OXR1) but not OX receptor 2 (OXR2). We further characterized the mechanism of CeA depolarization by OX as phospholipase C (PLC)- and sodium-calcium exchanger (NCX)- dependent. Selective chemogenetic stimulation of OX PeF fibers recapitulated OXR1 dependent depolarization of CeA neurons. We also observed that OXR1 activity modified presynaptic release of glutamate within the CeA. Finally, either systemic or intra-CeA perfusion of OXR1 antagonist reduced the expression of conditioned fear. Together, these data suggest the PeF-CeA orexinergic pathway can modulate conditioned fear through a signal transduction mechanism involving PLC and NCX activity and that selective OXR1 antagonism may be a putative treatment for fear-related disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.