Significance of GABAA 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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Bibliographic Details
Published in:International journal of molecular sciences 2021-11, Vol.22 (22), p.12456
Main Authors: Sakimoto, Yuya, Oo, Paw Min-Thein, Goshima, Makoto, Kanehisa, Itsuki, Tsukada, Yutaro, Mitsushima, Dai
Format: Article
Language:English
Subjects:
Alzheimer's disease
Autism
Epilepsy
Glutamatergic transmission
Hippocampus
Hyperactivity
Immobilization
Information processing
Kinases
Learning
Memory
Nervous system
Neurons
Peptides
Phosphorylation
Post traumatic stress disorder
Protein transport
Proteins
Review
Strengthening
Synapses
Synaptic plasticity
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
γ-Aminobutyric acid
γ-Aminobutyric acid A receptors
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Summary: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 GABAA (gamma-aminobutyric acid) receptor-mediated inhibitory synapses onto CA1 neurons. Recently we revealed that strengthening of GABAA 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 GABAA 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 GABAA receptor trafficking, synaptic E/I imbalance and neuronal excitability.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms222212456