Fujiwara Hideyuki, Zheng Meihong, Miyamoto Ai, Hoshino Osamu
Department of Intelligent Systems Engineering, Ibaraki University, 4-12-1 Nakanarusawa, Hitachi, Ibaraki 316-8511, Japan.
Cogn Process. 2011 May;12(2):151-9. doi: 10.1007/s10339-010-0375-7. Epub 2010 Nov 3.
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.
与年龄相关的皮质内抑制功能衰退可能是衰老过程中认知功能下降的基础。基于衰老导致细胞外（突触外）γ-氨基丁酸（GABA）基础浓度降低从而抑制皮质内抑制的假说，我们研究了基础浓度如何影响神经元的刺激诱发活动（作为信号）、持续自发活动（作为噪声）及其信噪比（S/N）。我们模拟了一个配备GABA转运系统的神经网络模型，该系统以神经元活动依赖的方式调节细胞外GABA浓度。基础浓度增加会使细胞外GABA增加，增强GABA介导的抑制性电流，并抑制持续自发活动，同时仍保持刺激诱发活动。这导致信噪比提高，为此GABA转运体的反转电位必须接近神经元的静息电位。在静息电位以上，由于转运体从细胞外空间过度摄取GABA，持续自发活动主要增强。在静息电位以下，由于GABA过度释放，刺激诱发活动主要受到抑制。我们认为，基础浓度降低导致细胞外GABA增加不足可能是衰老导致认知缺陷的可能原因之一，会增加持续自发的神经元活动作为噪声。如果GABA转运体的反转电位接近静息电位，它可能有助于提高信噪比。
