Phasic (fast) and tonic (sustained) inhibition of γ-aminobutyric acid (GABA) are fundamental for regulating day-to-day activities, neuronal excitability, and plasticity. However, the mechanisms and physiological functions of glial GABA transductions remain poorly understood. Here, we report that the AMsh glia in exhibit both phasic and tonic GABAergic signaling, which distinctively regulate olfactory adaptation and neuronal aging. Through genetic screening, we find that GABA permeates through bestrophin-9/-13/-14 anion channels from AMsh glia, which primarily activate the metabolic GABA receptor GBB-1 in the neighboring ASH sensory neurons. This tonic action of glial GABA regulates the age-associated changes of ASH neurons and olfactory responses via a conserved signaling pathway, inducing neuroprotection. In addition, the calcium-evoked, vesicular glial GABA release acts upon the ionotropic GABA receptor LGC-38 in ASH neurons to regulate olfactory adaptation. These findings underscore the fundamental significance of glial GABA in maintaining healthy aging and neuronal stability.

中文翻译：

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阶段性/强直性胶质细胞 GABA 对嗅觉适应和神经元衰老的差异转导

γ-氨基丁酸 (GABA) 的阶段性（快速）和强直性（持续）抑制对于调节日常活动、神经元兴奋性和可塑性至关重要。然而，神经胶质GABA转导的机制和生理功能仍然知之甚少。在这里，我们报告 AMsh 神经胶质细胞表现出阶段性和紧张性 GABA 信号，其独特地调节嗅觉适应和神经元衰老。通过基因筛选，我们发现GABA通过AMsh胶质细胞的bestropin-9/-13/-14阴离子通道渗透，主要激活邻近ASH感觉神经元中的代谢GABA受体GBB-1。神经胶质 GABA 的这种补品作用通过保守的信号通路调节 ASH 神经元和嗅觉反应与年龄相关的变化，从而诱导神经保护。此外，钙诱发的囊泡胶质 GABA 释放作用于 ASH 神经元中的离子型 GABA 受体 LGC-38，以调节嗅觉适应。这些发现强调了神经胶质 GABA 在维持健康衰老和神经元稳定性方面的根本意义。