TY - JOUR
T1 - Phasic/tonic glial GABA differentially transduce for olfactory adaptation and neuronal aging
AU - Cheng, Hankui
AU - Chen, Du
AU - Li, Xiao
AU - Al-Sheikh, Umar
AU - Duan, Duo
AU - Fan, Yuedan
AU - Zhu, Linhui
AU - Zeng, Wanxin
AU - Hu, Zhitao
AU - Tong, Xiajing
AU - Zhao, Guohua
AU - Zhang, Yongming
AU - Zou, Wenjuan
AU - Duan, Shumin
AU - Kang, Lijun
PY - 2024/5/1
Y1 - 2024/5/1
N2 - 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 Caenorhabditis elegans 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 GABAB 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 GABAA 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. © 2024 Elsevier Inc.
AB - 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 Caenorhabditis elegans 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 GABAB 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 GABAA 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. © 2024 Elsevier Inc.
KW - GABA
KW - GABAergic receptors
KW - glia-neuronal interaction
KW - neuronal aging
KW - olfactory adaptation
KW - phasic inhibition
KW - tonic inhibition
UR - http://www.scopus.com/inward/record.url?scp=85188545219&partnerID=8YFLogxK
UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85188545219&origin=recordpage
U2 - 10.1016/j.neuron.2024.02.006
DO - 10.1016/j.neuron.2024.02.006
M3 - RGC 21 - Publication in refereed journal
C2 - 38447577
SN - 0896-6273
VL - 112
SP - 1473
EP - 1486
JO - Neuron
JF - Neuron
IS - 9
ER -