ArticleThe international journal of neuropsychopharmacology2021
Astrocytic NMDA Receptors in the Basolateral Amygdala Contribute to Facilitation of Fear Extinction.
Article in The international journal of neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Investigation of Esketamine Administration During Surgical Procedures for the Alleviation of Postoperative Anxiety and Depression in Adolescent Patients: A Randomized Controlled Trial.Drug design, development and therapy · 2026Trial
- Calcium Signaling in Astrocytes and Its Role in the Central Nervous System Injury.Molecular neurobiology · 2025Review
- Review
- Stress Sensitization of Neurons in the Dentate Gyrus Is Dependent on Neuronal Interleukin-1 Receptor Signaling and Is Associated with Increased Synaptic Plasticity, Perineuronal Nets, and Excitatory/Inhibitory Input Imbalance.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Chronic postoperative pain induces contextual fear extinction dysfunction through hippocampal NMDAR/BDNF/TrkB signaling pathway in mice.Translational psychiatry · 2025Article
- The Role of Basolateral Amygdala and Medial Prefrontal Cortex in Fear: A Systematic Review.Cureus · 2025Review
- EphrinB2 in excitatory neurons and astrocytes in the basolateral amygdala controls long-term fear memory formation.Communications biology · 2024Article
- Astrocytic transcriptional and epigenetic mechanisms of drug addiction.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Molecular mechanisms underlying sex and treatment-dependent differences in an animal model of cue-exposure therapy for cocaine relapse prevention.Frontiers in neuroscience · 2024Article
- GluN2D Subunit in Parvalbumin Interneurons Regulates Prefrontal Cortex Feedforward Inhibitory Circuit and Molecular Networks Relevant to Schizophrenia.Biological psychiatry · 2023Article
- Basolateral Amygdala Astrocytes Are Engaged by the Acquisition and Expression of a Contextual Fear Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Update on neurobiological mechanisms of fear: illuminating the direction of mechanism exploration and treatment development of trauma and fear-related disorders.Frontiers in behavioral neuroscience · 2023Review
- Chronic intermittent hypoxia enhances glycinergic inhibition in nucleus tractus solitarius.Journal of neurophysiology · 2022Article
- Discovery of (Frontiers in chemistry · 2022Article
- From Synapses to Circuits, Astrocytes Regulate Behavior.Frontiers in neural circuits · 2021Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEnhancement of N-methyl-D-aspartate (NMDA) receptor function using glycine-site agonist D-cycloserine is known to facilitate fear extinction, providing a means to augment cognitive behavioral therapy in anxiety disorders. A novel class of glycine-site agonists has recently been identified, and we have found that the prototype, AICP, is more effective than D-cycloserine in modulating neuronal function.
methodsUsing novel glycine-site agonist AICP, local infusion studies, and genetic models, we elucidated the role of GluN2C-containing receptors in fear extinction.
resultsWe tested the effect of intracerebroventricular injection of AICP on fear extinction and found a robust facilitation of fear extinction. This effect was dependent on GluN2C subunit, consistent with superagonist action of AICP at GluN2C-containing receptors. Local infusion studies in wild-type and GluN2C knockout mice suggested that AICP produces its effect via GluN2C-containing receptors in the basolateral amygdala (BLA). Furthermore, consistent with astrocytic expression of GluN2C subunit in the amygdala, we found that AICP did not facilitate fear extinction in mice with conditional deletion of obligatory GluN1 subunit from astrocytes. Importantly, chemogenetic activation of astrocytes in the basolateral amygdala facilitated fear extinction. Acutely, AICP was found to facilitate excitatory neurotransmission in the BLA via presynaptic GluN2C-dependent mechanism. Immunohistochemical studies suggest that AICP-mediated facilitation of fear extinction involves synaptic insertion of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor GluA1 subunit.
conclusionThese results identify a unique role of astrocytic NMDA receptors composed of GluN2C subunit in extinction of conditioned fear memory and demonstrate that further development of recently identified superagonists of GluN2C-containing receptors may have utility for anxiety 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.