Role of cortical N-methyl-D-aspartate receptors in auditory sensory memory and mismatch negativity generation: implications for schizophrenia.
Open accessAbstract
Working memory refers to the ability of the brain to store and manipulate information over brief time periods, ranging from seconds to minutes. As opposed to long-term memory, which is critically dependent upon hippocampal processing, critical substrates for working memory are distributed in a modality-specific fashion throughout cortex. N-methyl-D-aspartate (NMDA) receptors play a crucial role in the initiation of long-term memory. Neurochemical mechanisms underlying the transient memory storage required for working memory, however, remain obscure. Auditory sensory memory, which refers to the ability of the brain to retain transient representations of the physical features (e.g., pitch) of simple auditory stimuli for periods of up to approximately 30 sec, represents one of the simplest components of the brain working memory system. Functioning of the auditory sensory memory system is indexed by the generation of a well-defined event-related potential, termed mismatch negativity (MMN). MMN can thus be used as an objective index of auditory sensory memory functioning and a probe for investigating underlying neurochemical mechanisms. Monkeys generate cortical activity in response to deviant stimuli that closely resembles human MMN. This study uses a combination of intracortical recording and pharmacological micromanipulations in awake monkeys to demonstrate that both competitive and noncompetitive NMDA antagonists block the generation of MMN without affecting prior obligatory activity in primary auditory cortex. These findings suggest that, on a neurophysiological level, MMN represents selective current flow through open, unblocked NMDA channels. Furthermore, they suggest a crucial role of cortical NMDA receptors in the assessment of stimulus familiarity/unfamiliarity, which is a key process underlying working memory performance.
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- Authors
- Javitt, D. C., Steinschneider, M., Schroeder, C. E., & Arezzo, J. C.
- Affiliations
- Albert Einstein College of Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1996-10-15
- Volume
- 93
- Issue
- 21
- Pages
- 11962-11967
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC38166
- OpenAlex
- W1996141026
- Cited by
- 662
- References
- 33
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 15 · 2023: 19 · 2022: 21 · 2021: 23 · 2020: 40 · 2019: 34 · 2018: 24 · 2017: 39 · 2016: 24 · 2015: 42 · 2014: 26 · 2013: 32 · 2012: 21
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r03mh046962-02, 2r01mh006723-28)
- U.S. Public Health Service
- National Institute of Mental Health (R01 MH06723, R03 MH46962)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroscience and Music Perception
- Keywords
- NMDA receptor, auditory sensory memory, mismatch negativity, working memory, schizophrenia, NMDA receptor antagonists, primary auditory cortex, event-related potentials, stimulus familiarity, cortical excitability
- MeSH terms
- Animals, Auditory Cortex, Auditory Perception, Bicuculline, Evoked Potentials, Hearing, Humans, Macaca fascicularis, Memory, Phencyclidine, Pipecolic Acids, Receptors, GABA-A, Schizophrenia, Schizophrenic Psychology, Time Factors, Receptors, N-Methyl-D-Aspartate, Excitatory Amino Acid Antagonists, GABA Antagonists, GABA-A Receptor Antagonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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