In schizophrenic patients, sensory tuning performance tends to be deteriorated (i.e., flattened sensory tuning), for which impaired intracortical tonic inhibition arising from a reduction in GABA concentration in extracellular space might be responsible. The δ subunit-containing GABA_A receptor, located on extrasynaptic sites, is known to be involved in mediating tonic inhibitory currents in cortical pyramidal cells and is considered to be one of the beneficial therapeutic targets for the treatment of schizophrenia. The transporter GAT-1 in glial (astrocytic) membrane controls concentration of GABA molecules by removing them from extracellular space. We speculated that the upregulation of extrasynaptic receptors might compensate for the impaired tonic inhibition and thus improve their sensory tuning performance, in which the astrocytic GABA transporter might play an important role. To test our hypothesis, we simulated a schizophrenic neural network model with a GABAergic gliotransmission (i.e., GABA transport by transporters embedded in astrocytic membranes) mechanism that modulates local ambient (extracellular) GABA levels in a neuronal activity-dependent manner. Upregulating extrasynaptic GABA receptors compensated the impaired tonic inhibition and sharpened the sensory tuning, provided that ambient GABA molecules around stimulus-sensitive pyramidal cells were actively removed during sensory stimulation. We suggest that the upregulation of extrasynaptic GABA receptors can improve the performance of sensory tuning in schizophrenic patients, for which spatiotemporal regulation of ambient GABA concentration by gliotransmission may be crucial.

中文翻译：

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通过神经胶质传递对细胞外空间中 GABA 浓度的时空调节对于突触外受体介导的精神分裂症感觉调节性能的改善至关重要。

在精神分裂症患者中，感觉调节性能趋于恶化（即感觉调节变平），这可能是由于细胞外空间 GABA 浓度降低导致皮层内强直抑制受损的原因。所述δ GAB含亚基-甲_甲位于突触外位点的受体，已知参与介导皮质锥体细胞中的强直抑制电流，被认为是治疗精神分裂症的有益治疗靶点之一。神经胶质（星形细胞）膜中的转运蛋白 GAT-1 通过将 GABA 分子从细胞外空间移除来控制 GABA 分子的浓度。我们推测突触外受体的上调可能补偿受损的强直抑制，从而改善它们的感觉调节性能，其中星形胶质细胞 GABA 转运蛋白可能发挥重要作用。为了验证我们的假设，我们模拟了一个带有 GABA 能神经胶质传递的精神分裂症神经网络模型（即，GABA 通过嵌入星形细胞膜的转运蛋白转运）机制，以神经元活动依赖性方式调节局部环境（细胞外）GABA 水平。上调突触外 GABA 受体可补偿受损的强直抑制并增强感觉调节，前提是在感觉刺激期间主动去除刺激敏感锥体细胞周围的环境 GABA 分子。我们建议突触外 GABA 受体的上调可以改善精神分裂症患者的感觉调节性能，因此通过神经胶质传递对环境 GABA 浓度的时空调节可能是至关重要的。前提是在感觉刺激期间主动去除刺激敏感锥体细胞周围的环境 GABA 分子。我们建议突触外 GABA 受体的上调可以改善精神分裂症患者的感觉调节性能，因此通过神经胶质传递对环境 GABA 浓度的时空调节可能是至关重要的。前提是在感觉刺激期间主动去除刺激敏感锥体细胞周围的环境 GABA 分子。我们建议突触外 GABA 受体的上调可以改善精神分裂症患者的感觉调节性能，因此通过神经胶质传递对环境 GABA 浓度的时空调节可能是至关重要的。