Significance of GABA<sub>A</sub> Receptor for Cognitive Function and Hippocampal Pathology

The hippocampus is a primary area for contextual memory, known to process spatiotemporal information within a specific episode. Long-term strengthening of glutamatergic transmission is a mechanism of contextual learning in the dorsal cornu ammonis 1 (CA1) area of the hippocampus. CA1-specific immobi...

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Autores principales:	Yuya Sakimoto, Paw Min-Thein Oo, Makoto Goshima, Itsuki Kanehisa, Yutaro Tsukada, Dai Mitsushima
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	AMPA receptor GABA<sub>A</sub> receptor contextual learning synaptic plasticity Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/90f9db50795243e595ecfb658e7d67ce
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spelling	oai:doaj.org-article:90f9db50795243e595ecfb658e7d67ce2021-11-25T17:56:49ZSignificance of GABA<sub>A</sub> Receptor for Cognitive Function and Hippocampal Pathology10.3390/ijms2222124561422-00671661-6596https://doaj.org/article/90f9db50795243e595ecfb658e7d67ce2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12456https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The hippocampus is a primary area for contextual memory, known to process spatiotemporal information within a specific episode. Long-term strengthening of glutamatergic transmission is a mechanism of contextual learning in the dorsal cornu ammonis 1 (CA1) area of the hippocampus. CA1-specific immobilization or blockade of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor delivery can impair learning performance, indicating a causal relationship between learning and receptor delivery into the synapse. Moreover, contextual learning also strengthens GABA<sub>A</sub> (gamma-aminobutyric acid) receptor-mediated inhibitory synapses onto CA1 neurons. Recently we revealed that strengthening of GABA<sub>A</sub> receptor-mediated inhibitory synapses preceded excitatory synaptic plasticity after contextual learning, resulting in a reduced synaptic excitatory/inhibitory (E/I) input balance that returned to pretraining levels within 10 min. The faster plasticity at inhibitory synapses may allow encoding a contextual memory and prevent cognitive dysfunction in various hippocampal pathologies. In this review, we focus on the dynamic changes of GABA<sub>A</sub> receptor mediated-synaptic currents after contextual learning and the intracellular mechanism underlying rapid inhibitory synaptic plasticity. In addition, we discuss that several pathologies, such as Alzheimer’s disease, autism spectrum disorders and epilepsy are characterized by alterations in GABA<sub>A</sub> receptor trafficking, synaptic E/I imbalance and neuronal excitability.Yuya SakimotoPaw Min-Thein OoMakoto GoshimaItsuki KanehisaYutaro TsukadaDai MitsushimaMDPI AGarticleAMPA receptorGABA<sub>A</sub> receptorcontextual learningsynaptic plasticityBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12456, p 12456 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AMPA receptor GABA<sub>A</sub> receptor contextual learning synaptic plasticity Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	AMPA receptor GABA<sub>A</sub> receptor contextual learning synaptic plasticity Biology (General) QH301-705.5 Chemistry QD1-999 Yuya Sakimoto Paw Min-Thein Oo Makoto Goshima Itsuki Kanehisa Yutaro Tsukada Dai Mitsushima Significance of GABA<sub>A</sub> Receptor for Cognitive Function and Hippocampal Pathology
description	The hippocampus is a primary area for contextual memory, known to process spatiotemporal information within a specific episode. Long-term strengthening of glutamatergic transmission is a mechanism of contextual learning in the dorsal cornu ammonis 1 (CA1) area of the hippocampus. CA1-specific immobilization or blockade of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor delivery can impair learning performance, indicating a causal relationship between learning and receptor delivery into the synapse. Moreover, contextual learning also strengthens GABA<sub>A</sub> (gamma-aminobutyric acid) receptor-mediated inhibitory synapses onto CA1 neurons. Recently we revealed that strengthening of GABA<sub>A</sub> receptor-mediated inhibitory synapses preceded excitatory synaptic plasticity after contextual learning, resulting in a reduced synaptic excitatory/inhibitory (E/I) input balance that returned to pretraining levels within 10 min. The faster plasticity at inhibitory synapses may allow encoding a contextual memory and prevent cognitive dysfunction in various hippocampal pathologies. In this review, we focus on the dynamic changes of GABA<sub>A</sub> receptor mediated-synaptic currents after contextual learning and the intracellular mechanism underlying rapid inhibitory synaptic plasticity. In addition, we discuss that several pathologies, such as Alzheimer’s disease, autism spectrum disorders and epilepsy are characterized by alterations in GABA<sub>A</sub> receptor trafficking, synaptic E/I imbalance and neuronal excitability.
format	article
author	Yuya Sakimoto Paw Min-Thein Oo Makoto Goshima Itsuki Kanehisa Yutaro Tsukada Dai Mitsushima
author_facet	Yuya Sakimoto Paw Min-Thein Oo Makoto Goshima Itsuki Kanehisa Yutaro Tsukada Dai Mitsushima
author_sort	Yuya Sakimoto
title	Significance of GABA<sub>A</sub> Receptor for Cognitive Function and Hippocampal Pathology
title_short	Significance of GABA<sub>A</sub> Receptor for Cognitive Function and Hippocampal Pathology
title_full	Significance of GABA<sub>A</sub> Receptor for Cognitive Function and Hippocampal Pathology
title_fullStr	Significance of GABA<sub>A</sub> Receptor for Cognitive Function and Hippocampal Pathology
title_full_unstemmed	Significance of GABA<sub>A</sub> Receptor for Cognitive Function and Hippocampal Pathology
title_sort	significance of gaba<sub>a</sub> receptor for cognitive function and hippocampal pathology
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/90f9db50795243e595ecfb658e7d67ce
work_keys_str_mv	AT yuyasakimoto significanceofgabasubasubreceptorforcognitivefunctionandhippocampalpathology AT pawmintheinoo significanceofgabasubasubreceptorforcognitivefunctionandhippocampalpathology AT makotogoshima significanceofgabasubasubreceptorforcognitivefunctionandhippocampalpathology AT itsukikanehisa significanceofgabasubasubreceptorforcognitivefunctionandhippocampalpathology AT yutarotsukada significanceofgabasubasubreceptorforcognitivefunctionandhippocampalpathology AT daimitsushima significanceofgabasubasubreceptorforcognitivefunctionandhippocampalpathology
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Significance of GABA<sub>A</sub> Receptor for Cognitive Function and Hippocampal Pathology

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