Until recently, glia, which exceeds the number of neurons, was considered to only have supportive roles in the central nervous system, providing homeostatic controls and metabolic supports. However, recent studies suggest that glia interacts with neurons and plays active roles in information processing within neuronal circuits. To elucidate how glia contributes to neuronal information processing, we simulated a sensory neuron-glia (neuron-astrocyte) network model. It was investigated in association with ambient (extracellular) GABA level, because the astrocyte has a major role in removing extracellular GABA molecules. In the network model, transporters, embedded in plasma membranes of astrocytes, modulated local ambient GABA levels by actively removing extracellular GABA molecules which persistently acted on receptors in membranes outside synapses and provided pyramidal cells with inhibitory currents. Gap-junction coupling between astrocytes mediated a concordant decrease in local ambient GABA levels, which solicited a prompt population response of pyramidal cells (i.e., activation of an ensemble of pyramidal cells) to a sensory stimulus. As a consequence, the reaction time of a motor network, to which axons of pyramidal cells of the sensory network project, to the sensory stimulus was shortened. We suggest that the astrocytic gap-junction coupling may assist in organizing dynamic cell assemblies by coordinating a reduction in local ambient GABA levels, thereby shortening reaction time to sensory stimulation.
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http://dx.doi.org/10.1007/s00422-019-00793-x | DOI Listing |
Nat Commun
December 2024
Department of Ophthalmology, Columbia University, New York, NY, USA.
Best1 and Best2 are two members of the bestrophin family of anion channels critically involved in the prevention of retinal degeneration and maintenance of intraocular pressure, respectively. Here, we solved glutamate- and γ-aminobutyric acid (GABA)-bound Best2 structures, which delineate an intracellular glutamate binding site and an extracellular GABA binding site on Best2, respectively, identified extracellular GABA as a permeable activator of Best2, and elucidated the co-regulation of Best2 by glutamate, GABA and glutamine synthetase in vivo. We further identified multiple small molecules as activators of the bestrophin channels.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Biochemistry, Duke University School of Medicine, Durham, NC, 27710, USA.
The current opioid crisis urgently calls for developing non-addictive pain medications. Progress has been slow, highlighting the need to uncover targets with unique mechanisms of action. Extracellular adenosine alleviates pain by activating the adenosine A1 receptor (A1R).
View Article and Find Full Text PDFAnn Clin Transl Neurol
December 2024
Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P. R. China.
Background: Variants in the GABRA2 gene, which encodes the α2 subunit of the γ-aminobutyric acid A receptor, have been linked to a rare form of developmental and epileptic encephalopathy (DEE) referred to as DEE78. Only eight patients have been reported globally. This study presents the clinical presentation and genetic analysis of a Chinese family with a child diagnosed with DEE78, due to a novel GABRA2 variant.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Clinical Medicine, North Sichuang Medical College, Nanchong, 63700, Sichuan Province, China.
Abdominal aortic aneurysm is a potentially fatal vascular inflammatory disease characterized by infiltration of various inflammatory cells.The GABA-A receptor is expressed in many inflammatory cells such as macrophages and T cells and has anti-inflammatory and antioxidant effects. Therefore, the GABA-A receptor may become a potential therapeutic target for abdominal aortic aneurysms.
View Article and Find Full Text PDFJ Physiol
December 2024
Department of Neuroscience and Physiology, NYU Grossman School of Medicine, New York, NY, USA.
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