ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2021
AMPA and NMDA Receptor Trafficking at Cocaine-Generated Synapses.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 30 citations in OpenAlex.
- The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026Review
- Downregulation of integrin α3 in ADHD mirrored in mutant mouse model by dopamine-dependent hippocampal AMPAR expression.Molecular psychiatry · 2026Article
- Population-level neural rejuvenation dynamics in addiction: a computational framework for understanding developmental plasticity reactivation.Frontiers in computational neuroscience · 2026Article
- Activation of silent synapses driven by emerging technologies: mechanisms, disease associations, and prospects for clinical translation.Frontiers in synaptic neuroscience · 2026Review
- Astrocytic CREB regulates transcriptomic, neuronal, and behavioral responses to cocaine.Science advances · 2025Article
- Increased NMDAR activity and GluN2A-NMDAR silent synapse expansion induced by chronic benzodiazepine treatment.Neuropharmacology · 2025Article
- Functional and Structural Plasticity in Cocaine-Seeking Ensembles of the Nucleus Accumbens Core.bioRxiv : the preprint server for biology · 2025Article
- Inhibiting SNX14 Alleviates Epileptic Seizures by Regulating GluA2 Degradation via the Lysosomal Pathway.Molecular neurobiology · 2025Article
- Cocaine-induced gene regulation in D1 and D2 neuronal ensembles of the nucleus accumbens.Communications biology · 2025Article
- CPEB3 can regulate seizure susceptibility by inhibiting the transcriptional activity of STAT3 on NMDARs expression.Molecular medicine (Cambridge, Mass.) · 2025Article
- GluN2B-mediated regulation of silent synapses for receptor specification and addiction memory.Experimental & molecular medicine · 2025Article
- Synaptic Plasticity Linked to Ionotropic Glutamate Receptors After Nicotine Exposure.Current neuropharmacology · 2025Review
- Replication and extension of the subregion selectivity of glutamate-related changes within the nucleus accumbens associated with the incubation of cocaine-craving.Pharmacology, biochemistry, and behavior · 2024Article
- Decoding cocaine-induced proteomic adaptations in the mouse nucleus accumbens.Science signaling · 2024Article
- Roles of lncLingo2 and its derived miR-876-5p in the acquisition of opioid reinforcement.Addiction biology · 2024Article
- Membrane excitability of nucleus accumbens neurons gates the incubation of cocaine craving.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- KCTD13-mediated ubiquitination and degradation of GluN1 regulates excitatory synaptic transmission and seizure susceptibility.Cell death and differentiation · 2023Article
- Intrusive thinking: Circuit and synaptic mechanisms of a transdiagnostic psychiatric symptom.Neuroscience and biobehavioral reviews · 2023Review
- Corticospinal circuit neuroplasticity may involve silent synapses: Implications for functional recovery facilitated by neuromodulation after spinal cord injury.IBRO neuroscience reports · 2023Article
- Dysregulation of AMPA Receptor Trafficking and Intracellular Vesicular Sorting in the Prefrontal Cortex of Dopamine Transporter Knock-Out Rats.Biomolecules · 2023Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Cocaine experience generates AMPA receptor (AMPAR)-silent synapses in the nucleus accumbens (NAc), which are thought to be new synaptic contacts enriched in GluN2B-containing NMDA receptors (NMDARs). After drug withdrawal, some of these synapses mature by recruiting AMPARs, strengthening the newly established synaptic transmission. Silent synapse generation and maturation are two consecutive cellular steps through which NAc circuits are profoundly remodeled to promote cue-induced cocaine seeking after drug withdrawal. However, the basic cellular processes that mediate these two critical steps remains underexplored. Using a combination of electrophysiology, viral-mediated gene transfer, and confocal imaging in male rats as well as knock-in (KI) mice of both sexes, our current study characterized the dynamic roles played by AMPARs and NMDARs in generation and maturation of silent synapses on NAc medium spiny neurons after cocaine self-administration and withdrawal. We report that cocaine-induced generation of silent synapses not only required synaptic insertion of GluN2B-containing NMDARs, but also, counterintuitively, involved insertion of AMPARs, which subsequently internalized, resulting in the AMPAR-silent state on withdrawal day 1. Furthermore, GluN2B NMDARs functioned to maintain these cocaine-generated synapses in the AMPAR-silent state during drug withdrawal, until they were replaced by nonGluN2B NMDARs, a switch that allowed AMPAR recruitment and maturation of silent synapses. These results reveal dynamic interactions between AMPARs and NMDARs during the generation and maturation of silent synapses after cocaine experience and provide a mechanistic basis through which new synaptic contacts and possibly new neural network patterns created by these synapses can be manipulated for therapeutic benefit.
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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.