Identity of endogenous NMDAR glycine site agonist in amygdala is determined by synaptic activity level
Open accessAbstract
Mechanisms of N-methyl-D-aspartate receptor-dependent synaptic plasticity contribute to the acquisition and retention of conditioned fear memory. However, synaptic rules which may determine the extent of N-methyl-D-aspartate receptor activation in the amygdala, a key structure implicated in fear learning, remain unknown. Here we show that the identity of the N-methyl-D-aspartate receptor glycine site agonist at synapses in the lateral nucleus of the amygdala may depend on the level of synaptic activation. Tonic activation of N-methyl-D-aspartate receptors at synapses in the amygdala under low activity conditions is supported by ambient D-serine, whereas glycine may be released from astrocytes in response to afferent impulses. The release of glycine may decode the increases in afferent activity levels into enhanced N-methyl-D-aspartate receptor-mediated synaptic events, serving an essential function in the induction of N-methyl-D-aspartate receptor-dependent long-term potentiation in fear conditioning pathways.
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Published studies have revealed beneficial effects of NAC in schizophrenia patients as an add-on to maintenance medication.
“Published studies have revealed beneficial effects in schizophrenia patients as an add-on to maintenance medication [100][101][102][103] and ongoing studies are following up their results and including additional metrics of efficacy such as brain GSH imaging in order to reflect the BBB permeability analyses of NAC that have been performed in rodents 104 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [101]
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References 52 · Cited by 82
- Authors
- Li, Y., Sacchi, S., Pollegioni, L., Basu, A. C., Coyle, J. T., & Bolshakov, V. Y.
- Affiliations
- Harvard University (US)
- University of Insubria (IT)
- Corresponding author
- Bolshakov, Vadim Y.
- Venue
- Nature Communications
- Published
- 2013-04-23
- Volume
- 4
- Issue
- 1
- Pages
- 1760-1760
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3641574
- OpenAlex
- W2114197624
- Cited by
- 82
- References
- 52
- Citations by year
- 2025: 3 · 2024: 6 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 7 · 2019: 8 · 2018: 5 · 2017: 11 · 2016: 11 · 2015: 6 · 2014: 8 · 2013: 3
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- IrInSubria (University of Insubria) (submittedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Ministero dell’Istruzione, dell’Università e della Ricerca (2008N2FM4A_001)
- National Institutes of Health (W81XWH)
- National Institute of Mental Health (R01MH090464, P50MH060450, R01MH051290, MH083011, MH051290, R21MH083011, MH060450, MH090464)
- U.S. Army Medical Research Acquisition Activity
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- NMDA receptor, lateral amygdala, D-serine, glycine release, astrocytes, synaptic activity, fear conditioning, long-term potentiation, synaptic plasticity, glutamate
- MeSH terms
- Amygdala, Animals, Astrocytes, D-Amino-Acid Oxidase, Female, Gliotoxin, Glycine, Male, Serine, Synapses, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Mice, Rats, In Vitro Techniques
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