Cited by 74Nicotinic Acetylcholine Receptors StudySchizophrenia research and treatmentNeuroscience and Neuropharmacology Research

Glutamate and nicotinic receptor interactions in working memory: importance for the cognitive impairment of schizophrenia

Timofeeva, O.A., Levin, E.D.·2011·Neuroscience

Abstract

This article reaches across disciplines to correlate results in molecular, cellular, behavioral, and clinical research to develop a more complete picture of how working memory (WM) functions. It identifies a new idea that deserves further investigation. NMDA glutamate receptors (NMDAR) are critical for memory function. NMDAR inhibition effectively reproduces principal manifestations of schizophrenia (SP), such as WM impairment and GABAergic deficit (mainly reduction of glutamic acid decarboxylase 67 (GAD67) and parvalbumin (PV) content). Nicotine and selective α7 nicotinic acetylcholine receptor (nAChR) agonists reduce WM impairments in patients with SP and reverse WM deficits in animals treated with NMDAR antagonists. The mechanism of this effect is unknown. Importantly, WM recovery occurs even before restoration of NMDAR blockade-induced molecular alterations, including reduced GAD67 in interneurons. Our insight into the cognitive-enhancing effect of α7 nAChR agonists, particularly in the animal models of SP, combines reviews of recent findings on glutamate and nicotinic receptor expression in the neuronal circuits involved in WM, the properties of these receptors, their implication in WM regulation, generation of rhythmic neuronal activity, resulting in a proposed hypothesis for further investigations. We suggest that (1) cortical/hippocampal interneurons, particularly PV positive, play a crucial role in WM and that impairment of these cells in SP could be behind the WM deficit; (2) activation of α7 nAChRs could restore calcium signaling and intrinsic properties of these interneurons, and associated with these events, computational capacity, gamma rhythmic activity, and WM would also be restored.

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Crossref · 10.1016/j.neuroscience.2011.08.038

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196 of 196 references verified0 citation errors · 0 not checkable

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  • In schizophrenia, NMDA receptors are believed to be hypo-functioning, and NMDA receptor inhibition reproduces many schizophrenia symptoms.

    “In schizophrenia, NMDA receptors are believed to be hypo-functioning, and the inhibition of NMDA receptors recapitulates many of the symptoms of schizophrenia [104, 122, 123].”

    From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [104]

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Authors
Timofeeva, O. A., & Levin, E. D.
Affiliations
Duke University (US)
Venue
Neuroscience
Publisher
Elsevier BV
Published
2011-11
Volume
195
Pages
21-36
ISSN
0306-4522 (ISSN-L)
OpenAlex
W1978511436
Cited by
74
References
196
Citations by year
2025: 3 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 6 · 2018: 1 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 14 · 2013: 13 · 2012: 13
FWCI
1.19
Type
journal article
Language
en
Open access
closed
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
working memory, schizophrenia, NMDA receptor, glutamate receptors, nicotinic acetylcholine receptors, GAD67, parvalbumin, cortical interneurons, hippocampal interneurons, gamma oscillations, calcium signaling, cognitive impairment
MeSH terms
Animals, Brain, Cognition Disorders, Humans, Memory, Short-Term, Receptors, Nicotinic, Schizophrenia, Receptors, Glutamate

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