Abstract
Age-related degeneration of intracortical inhibition could underlie declines in cognitive function during senescence. Based on a hypothesis that a decrease in basal concentration of ambient (extrasynaptic) GABA with aging leads to depressing intracortical inhibition, we investigated how the basal concentration affects stimulus-evoked activity (as signal), ongoing-spontaneous activity (as noise) of neurons and their (signal-to-noise) ratio S/N. We simulated a neural network model equipped with a GABA transport system that regulates ambient GABA concentration in a neuronal activity-dependent manner. An increase in basal concentration augmented ambient GABA, increased GABA-mediated inhibitory current, and depressed ongoing-spontaneous activity while still keeping stimulus-evoked activity. This led to S/N improvement, for which it was necessary for the reversal potential of GABA transporter to be close to the resting potential of neurons. Above the resting potential, ongoing-spontaneous activity was predominantly enhanced due to excessive GABA-uptake from the extracellular space by transporters. Below the resting potential, stimulus-evoked activity was predominantly depressed, caused by excessive GABA-release. We suggest that the insufficient augmentation of ambient GABA due to a decrease in its basal concentration may be one of the possible causes of cognitive deficit with aging, increasing ongoing-spontaneous neuronal activity as noise. GABA transporter may contribute to improving S/N, provided that its reversal potential is close to the resting potential.
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Discussions with Tomoya Suzuki are gratefully acknowledged. We express our gratitude to anonymous reviewers for giving us valuable comments and suggestions on the earlier drafts.
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Fujiwara, H., Zheng, M., Miyamoto, A. et al. Insufficient augmentation of ambient GABA responsible for age-related cognitive deficit. Cogn Process 12, 151–159 (2011). https://doi.org/10.1007/s10339-010-0375-7
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DOI: https://doi.org/10.1007/s10339-010-0375-7