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Beyond NMDA Receptors: Homeostasis at the Glutamate Tripartite Synapse and Its Contributions to Cognitive Dysfunction in Schizophrenia

Cognitive deficits are core symptoms of schizophrenia but remain poorly addressed by dopamine-based antipsychotic medications. Glutamate abnormalities are implicated in schizophrenia-related cognitive deficits. While the role of the NMDA receptor has been extensively studied, less attention was give...

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Autores principales: Bauminger, Hagar, Gaisler-Salomon, Inna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368772/
https://www.ncbi.nlm.nih.gov/pubmed/35955750
http://dx.doi.org/10.3390/ijms23158617
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author Bauminger, Hagar
Gaisler-Salomon, Inna
author_facet Bauminger, Hagar
Gaisler-Salomon, Inna
author_sort Bauminger, Hagar
collection PubMed
description Cognitive deficits are core symptoms of schizophrenia but remain poorly addressed by dopamine-based antipsychotic medications. Glutamate abnormalities are implicated in schizophrenia-related cognitive deficits. While the role of the NMDA receptor has been extensively studied, less attention was given to other components that control glutamate homeostasis. Glutamate dynamics at the tripartite synapse include presynaptic and postsynaptic components and are tightly regulated by neuron–astrocyte crosstalk. Here, we delineate the role of glutamate homeostasis at the tripartite synapse in schizophrenia-related cognitive dysfunction. We focus on cognitive domains that can be readily measured in humans and rodents, i.e., working memory, recognition memory, cognitive flexibility, and response inhibition. We describe tasks used to measure cognitive function in these domains in humans and rodents, and the relevance of glutamate alterations in these domains. Next, we delve into glutamate tripartite synaptic components and summarize findings that implicate the relevance of these components to specific cognitive domains. These collective findings indicate that neuron–astrocyte crosstalk at the tripartite synapse is essential for cognition, and that pre- and postsynaptic components play a critical role in maintaining glutamate homeostasis and cognitive well-being. The contribution of these components to cognitive function should be considered in order to better understand the role played by glutamate signaling in cognition and develop efficient pharmacological treatment avenues for schizophrenia treatment-resistant symptoms.
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spelling pubmed-93687722022-08-12 Beyond NMDA Receptors: Homeostasis at the Glutamate Tripartite Synapse and Its Contributions to Cognitive Dysfunction in Schizophrenia Bauminger, Hagar Gaisler-Salomon, Inna Int J Mol Sci Review Cognitive deficits are core symptoms of schizophrenia but remain poorly addressed by dopamine-based antipsychotic medications. Glutamate abnormalities are implicated in schizophrenia-related cognitive deficits. While the role of the NMDA receptor has been extensively studied, less attention was given to other components that control glutamate homeostasis. Glutamate dynamics at the tripartite synapse include presynaptic and postsynaptic components and are tightly regulated by neuron–astrocyte crosstalk. Here, we delineate the role of glutamate homeostasis at the tripartite synapse in schizophrenia-related cognitive dysfunction. We focus on cognitive domains that can be readily measured in humans and rodents, i.e., working memory, recognition memory, cognitive flexibility, and response inhibition. We describe tasks used to measure cognitive function in these domains in humans and rodents, and the relevance of glutamate alterations in these domains. Next, we delve into glutamate tripartite synaptic components and summarize findings that implicate the relevance of these components to specific cognitive domains. These collective findings indicate that neuron–astrocyte crosstalk at the tripartite synapse is essential for cognition, and that pre- and postsynaptic components play a critical role in maintaining glutamate homeostasis and cognitive well-being. The contribution of these components to cognitive function should be considered in order to better understand the role played by glutamate signaling in cognition and develop efficient pharmacological treatment avenues for schizophrenia treatment-resistant symptoms. MDPI 2022-08-03 /pmc/articles/PMC9368772/ /pubmed/35955750 http://dx.doi.org/10.3390/ijms23158617 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bauminger, Hagar
Gaisler-Salomon, Inna
Beyond NMDA Receptors: Homeostasis at the Glutamate Tripartite Synapse and Its Contributions to Cognitive Dysfunction in Schizophrenia
title Beyond NMDA Receptors: Homeostasis at the Glutamate Tripartite Synapse and Its Contributions to Cognitive Dysfunction in Schizophrenia
title_full Beyond NMDA Receptors: Homeostasis at the Glutamate Tripartite Synapse and Its Contributions to Cognitive Dysfunction in Schizophrenia
title_fullStr Beyond NMDA Receptors: Homeostasis at the Glutamate Tripartite Synapse and Its Contributions to Cognitive Dysfunction in Schizophrenia
title_full_unstemmed Beyond NMDA Receptors: Homeostasis at the Glutamate Tripartite Synapse and Its Contributions to Cognitive Dysfunction in Schizophrenia
title_short Beyond NMDA Receptors: Homeostasis at the Glutamate Tripartite Synapse and Its Contributions to Cognitive Dysfunction in Schizophrenia
title_sort beyond nmda receptors: homeostasis at the glutamate tripartite synapse and its contributions to cognitive dysfunction in schizophrenia
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9368772/
https://www.ncbi.nlm.nih.gov/pubmed/35955750
http://dx.doi.org/10.3390/ijms23158617
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