ArticleNeuropharmacology2020
The kappa opioid receptor modulates GABA neuron excitability and synaptic transmission in midbrainprojections from the insular cortex.
Article in Neuropharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Kappa opioid receptor availability correlates with depressive symptom burden in chronic migraine: a preliminary investigation.The journal of headache and pain · 2026Article
- κ-Opioid Receptor Agonists as Robust Pain-Modulating Agents: Mechanisms and Therapeutic Potential in Pain Modulation.Journal of clinical medicine · 2025Review
- Opioid Receptors Modulate Inhibition within the Prefrontal Cortex through Dissociable Cellular and Molecular Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction.Current addiction reports · 2025Review
- Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states.Neuron · 2024Article
- Opioid modulation of prefrontal cortex cells and circuits.Neuropharmacology · 2024Review
- Forced Abstinence from Volitional Ethanol Intake Drives a Vulnerable Period of Hyperexcitability in BNST-Projecting Insular Cortex Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states.bioRxiv : the preprint server for biology · 2024Article
- Dynorphin / kappa-opioid receptor regulation of excitation-inhibition balance toggles afferent control of prefrontal cortical circuits in a pathway-specific manner.Molecular psychiatry · 2023Article
- Electroacupuncture alleviates the relapse of pain-related aversive memory by activating KOR and inhibiting GABAergic neurons in the insular cortex.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Insula Dynorphin and Kappa Opioid Receptor Systems Regulate Alcohol Drinking in a Sex-Specific Manner in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Shared Mechanisms of GABAergic and Opioidergic Transmission Regulate Corticolimbic Reward Systems and Cognitive Aspects of Motivational Behaviors.Brain sciences · 2023Review
- Involvement of Lateral Habenula Dysfunction in Repetitive Mild Traumatic Brain Injury-Induced Motivational Deficits.Journal of neurotrauma · 2023Article
- Transforming experiences: Neurobiology of memory updating/editing.Frontiers in systems neuroscience · 2023Review
- Dynorphin/Kappa-Opioid Receptor System Modulation of Cortical Circuitry.Handbook of experimental pharmacology · 2022Review
- Opioid Receptor-Mediated Regulation of Neurotransmission in the Brain.Frontiers in molecular neuroscience · 2022Review
- Neuropeptide System Regulation of Prefrontal Cortex Circuitry: Implications for Neuropsychiatric Disorders.Frontiers in neural circuits · 2022Review
- Mouse models of surgical and neuropathic pain produce distinct functional alterations to prodynorphin expressing neurons in the prelimbic cortex.Neurobiology of pain (Cambridge, Mass.)Article
- Mapping Kappa Opioid Receptor Binding in Titi Monkeys with [Molecular imagingArticle
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
As an integrative hub, the insular cortex (IC) translates external cues into interoceptive states that generate complex physiological, affective, and behavioral responses. However, the precise circuit and signaling mechanisms in the IC that modulate these processes are unknown. Here, we describe a midbrain-projecting microcircuit in the medial aspect of the agranular IC that signals through the Gαi/o-coupled kappa opioid receptor (KOR) and its endogenous ligand dynorphin (Dyn). Within this microcircuit, Dyn is robustly expressed in layer 2/3, while KOR is localized to deep layer 5, which sends a long-range projection to the substantia nigra (SN). Using ex vivo electrophysiology, we evaluated the functional impact of KOR signaling in layer 5 of the IC. We found that bath application of dynorphin decreased GABA release and increased glutamate release on IC-SN neurons, but did not alter their excitability. Conversely, dynorphin decreased the excitability of GABA neurons without altering synaptic transmission. Pretreatment with the KOR antagonist nor-BNI blocked the effects of dynorphin in IC-SN neurons and GABA neurons, indicating that the changes in synaptic transmission and excitability were selectively mediated through KOR. Selective inhibition of IC GABA neurons using a KOR-derived DREADD recapitulated these effects. This work provides insight into IC microcircuitry and indicates that Dyn/KOR signaling may act to directly reduce activity of layer 5 GABA neurons. In turn, KOR-driven inhibition of GABA promotes disinhibition of IC-SN neurons, which can modulate downstream circuits. Our findings present a potential mechanism whereby chronic upregulation of IC Dyn/KOR signaling can lead to altered subcortical function and downstream activity.
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Registered trials
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.