Mechanisms for acute stress-induced enhancement of glutamatergic transmission and working memory
Open accessAbstract
Corticosteroid stress hormones have a strong impact on the function of prefrontal cortex (PFC), a central region controlling cognition and emotion, though the underlying mechanisms are elusive. We found that behavioral stressor or short-term corticosterone treatment in vitro induces a delayed and sustained potentiation of the synaptic response and surface expression of N-methyl-D-aspartic acid receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in PFC pyramidal neurons through a mechanism depending on the induction of serum- and glucocorticoid-inducible kinase (SGK) and the activation of Rab4, which mediates receptor recycling between early endosomes and the plasma membrane. Working memory, a key function relying on glutamatergic transmission in PFC, is enhanced in acutely stressed animals through an SGK-dependent mechanism. These results suggest that acute stress, by activating glucocorticoid receptors, increases the trafficking and function of NMDARs and AMPARs through SGK/Rab4 signaling, which leads to the potentiated synaptic transmission, thereby facilitating cognitive processes mediated by the PFC.
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SGKs are involved in acute stress effects by enhancing Rab4-mediated trafficking of glutamate receptors from early endosomes to plasma membrane in PFC neurons.
“Serum-and glucocorticoid-inducible kinases (SGKs), an immediate early gene activated by stress hormone, is shown to be involved by enhancing Rab4-mediated trafficking of glutamate receptors from early endosomes to plasma membrane in PFC neurons 98,99.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [98]
Acute stress, via acting on GR, induces a delayed potentiation of NMDAR- and AMPAR-mediated synaptic currents, correlated with increased levels of synaptic NMDAR and AMPAR subunits.
“Acute stress, via acting on GR, also induces a delayed potentiation of NMDAR-and AMPAR-mediated synaptic currents, which is correlated with the increased level of synaptic NMDAR and AMPAR subunits 96,98.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [98]
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References 64 · Cited by 324
- Authors
- Yuen, E. Y., Liu, W., Karatsoreos, I. N., Ren, Y., Feng, J., McEwen, B. S., & Yan, Z.
- Affiliations
- University at Buffalo, State University of New York (US)
- Rockefeller University (US)
- Corresponding author
- Yan, Z
- Venue
- Molecular Psychiatry
- Published
- 2010-05-11
- Volume
- 16
- Issue
- 2
- Pages
- 156-170
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3108461
- OpenAlex
- W2024469079
- Cited by
- 324
- References
- 64
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 10 · 2023: 14 · 2022: 18 · 2021: 23 · 2020: 26 · 2019: 15 · 2018: 24 · 2017: 19 · 2016: 28 · 2015: 29 · 2014: 28 · 2013: 26 · 2012: 26
- FWCI
- 8.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH085774)
- National Institute of Neurological Disorders and Stroke (R01NS061856)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- acute stress, corticosterone, prefrontal cortex, glutamatergic neurotransmission, working memory, NMDA receptor, AMPA receptors, synaptic potentiation, SGK, Rab4, receptor trafficking, glucocorticoid receptor, pyramidal neurons, synaptic plasticity
- MeSH terms
- Serum-Glucocorticoid Regulated Kinases, Animals, Animals, Newborn, Biophysics, Cells, Cultured, Corticosterone, Dose-Response Relationship, Drug, Drug Interactions, Electric Stimulation, Gene Expression Regulation, Hormone Antagonists, Male, Memory, Short-Term, Synaptic Transmission, Peptides, Stress, Psychological, Time Factors, Transfection, Mifepristone, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Prefrontal Cortex, Receptors, Glutamate, Long-Term Potentiation, Immediate-Early Proteins, Pyramidal Cells, Patch-Clamp Techniques, Excitatory Amino Acid Agents, Glutamic Acid, Maze Learning, Excitatory Postsynaptic Potentials, rab GTP-Binding Proteins, RNA, Small Interfering, Green Fluorescent Proteins, Rats, In Vitro Techniques
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