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Insufficient augmentation of ambient GABA responsible for age-related cognitive deficit

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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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Acknowledgments

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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Authors and Affiliations

  1. Department of Intelligent Systems Engineering, Ibaraki University, 4-12-1 Nakanarusawa, Hitachi, Ibaraki, 316-8511, Japan

    Hideyuki Fujiwara & Osamu Hoshino

  2. Department of Psychology, Tsinghua University, Haidian District, Beijing, 100084, China

    Meihong Zheng

  3. Department of Psychology, University of Victoria, Victoria, BC, Canada

    Ai Miyamoto

Authors
  1. Hideyuki Fujiwara
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  2. Meihong Zheng
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  3. Ai Miyamoto
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  4. Osamu Hoshino
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Correspondence to Osamu Hoshino.

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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

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