Phasic/tonic glial GABA differentially transduce for olfactory adaptation and neuronal aging
Hankui Cheng1, Du Chen1, Xiao Li1
1Department of Neurology of the Fourth Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Yiwu 322000, China; MOE Frontier Science Center for Brain Science and Brain machine Integration, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310053, China.
Neuron
|March 6, 2024
Summary
Glial cells use both fast and sustained gamma-aminobutyric acid (GABA) signaling to control sensory neuron aging and adaptation. This glial GABA signaling pathway promotes neuroprotection and maintains neuronal stability.
Area of Science:
- Neuroscience
- Cell Biology
- Aging Research
Background:
- Glia play crucial roles in neuronal function, but glial gamma-aminobutyric acid (GABA) signaling mechanisms and functions are not well understood.
- Both phasic (fast) and tonic (sustained) inhibition by GABA are vital for regulating neuronal excitability, plasticity, and daily activities.
Purpose of the Study:
- To investigate the mechanisms and physiological roles of glial GABAergic signaling in Caenorhabditis elegans.
- To elucidate how glial GABA transduction influences sensory neuron function, adaptation, and aging.
Main Methods:
- Genetic screening in C. elegans to identify components of glial GABA signaling.
- Utilized electrophysiology and calcium imaging to study neuronal responses to glial GABA.
- Investigated the roles of specific GABA receptors (GABAB and GABAA) and anion channels in glial GABA transduction.
Main Results:
- AMsh glia in C. elegans exhibit both phasic and tonic GABAergic signaling.
- GABA released from glia permeates through bestrophin anion channels and activates the GBB-1 GABAB receptor in ASH sensory neurons.
- Tonic glial GABA signaling regulates age-associated changes in ASH neurons and olfactory responses, conferring neuroprotection.
- Vesicular release of glial GABA activates the LGC-38 GABAA receptor in ASH neurons, modulating olfactory adaptation.
Conclusions:
- Glial GABAergic signaling is fundamental for regulating sensory neuron adaptation and healthy neuronal aging.
- The identified glial GABA transduction pathway involving bestrophin channels and GABA receptors highlights a conserved mechanism for neuroprotection.
- These findings emphasize the critical role of glia in maintaining neuronal stability and function throughout the aging process.
