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 immobilization or blockade of alpha-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(A) (gamma-aminobutyric acid) receptor-mediated inhibitory synapses onto CA1 neurons. Recently we revealed that strengthening of GABA(A) 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(A) 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(A) receptor trafficking, synaptic E/I imbalance and neuronal excitability.

Automated summary

The hippocampus plays a key role in contextual memory, with long-term strengthening of glutamatergic transmission and enhancement of GABA(A) receptor-mediated inhibitory synapses after learning. Rapid plasticity at inhibitory synapses following contextual learning may facilitate encoding of memories and prevent cognitive dysfunction in hippocampal pathologies such as Alzheimer's disease, autism spectrum disorders, and epilepsy.