Department of Intelligent Systems Engineering, Ibaraki University, Hitachi, Ibaraki, Japan.
Neural Comput. 2011 Dec;23(12):3205-31. doi: 10.1162/NECO_a_00211. Epub 2011 Sep 15.
Experience-dependent synaptic plasticity characterizes the adaptable brain and is believed to be the cellular substrate for perceptual learning. A chemical agent such as gamma-aminobutyric acid (GABA) is known to affect synaptic alteration, perhaps gating perceptual learning. We examined whether and how ambient (extrasynaptic) GABA affects experience-dependent synaptic alteration. A cortical neural network model was simulated. Transporters on GABAergic interneurons regulate ambient GABA levels around their axonal target neurons by removing GABA from (forward transport) or releasing it into (reverse transport) the extracellular space. The ambient GABA provides neurons with tonic inhibitory currents by activating extrasynaptic GABA(a) receptors. During repeated exposures to the same stimulus, we modified the synaptic connection strength between principal cells in a spike-timing-dependent manner. This modulated the activity of GABAergic interneurons, and reduced or augmented ambient GABA concentration. Reduction in ambient GABA concentration led to slight depolarization (less than several millivolts) in ongoing-spontaneous membrane potential. This was a subthreshold neuronal behavior because ongoing-spontaneous spiking activity remained almost unchanged. The ongoing-spontaneous subthreshold depolarization improved a suprathreshold neuronal response. If the stimulus was long absent for perceptual learning, augmentation of ambient GABA concentration took place and the ongoing-spontaneous subthreshold depolarization was depressed. We suggest that a perceptual memory trace could be left in neuronal circuitry as an ongoing-spontaneous subthreshold membrane depolarization, which would allow that memory to be accessed easily afterward, whereas a trace of a memory that has not recently been retrieved fades away when the ongoing-spontaneous subthreshold membrane depolarization built by previous perceptual learning is depressed. This would lead that memory to be accessed with some difficulty. In the brain, ambient GABA, whose level could be regulated by transporter may have an important role in leaving memory trace for perceptual learning.
经验依赖性突触可塑性是大脑适应性的特征，被认为是知觉学习的细胞基础。众所周知，一种化学物质，如γ-氨基丁酸（GABA），可以影响突触变化，也许可以控制知觉学习。我们研究了环境（细胞外）GABA 是否以及如何影响经验依赖性突触变化。模拟了一个皮质神经网络模型。GABA 能中间神经元上的转运体通过从细胞外空间（正向转运）去除 GABA 或向其释放 GABA（反向转运）来调节其轴突靶神经元周围的环境 GABA 水平。环境 GABA 通过激活细胞外 GABA(a)受体为神经元提供紧张性抑制电流。在反复暴露于相同刺激的过程中，我们以时间依赖性的方式改变了主细胞之间的突触连接强度。这调节了 GABA 能中间神经元的活动，并减少或增加了环境 GABA 浓度。环境 GABA 浓度的降低导致持续自发性膜电位的轻微去极化（小于几个毫伏）。这是一种亚阈神经元行为，因为持续自发性放电活动几乎保持不变。持续自发性亚阈去极化改善了超阈值神经元反应。如果刺激长时间不存在以进行知觉学习，则会增加环境 GABA 浓度，并且持续自发性亚阈去极化被抑制。我们认为，神经元回路中的知觉记忆痕迹可以作为持续自发性亚阈膜去极化而留下，这使得随后很容易访问该记忆，而当以前的知觉学习所建立的持续自发性亚阈膜去极化被抑制时，没有最近检索到的记忆痕迹就会消失。这将导致该记忆难以访问。在大脑中，其水平可通过转运体调节的环境 GABA 可能在为知觉学习留下记忆痕迹方面具有重要作用。
