Extracellular GABA assisting in organizing dynamic cell assemblies to shorten reaction time to sensory stimulation.

Biol Cybern

Department of Intelligent Systems Engineering, Ibaraki University, 4-12-1 Nakanarusawa, Hitachi, Ibaraki, 316-8511, Japan.

Published: June 2019

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.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00422-019-00793-xDOI Listing

Publication Analysis

Top Keywords

extracellular gaba
16
pyramidal cells
16
reaction time
12
local ambient
12
ambient gaba
12
gaba levels
12
organizing dynamic
8
dynamic cell
8
cell assemblies
8
time sensory
8

Similar Publications

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 PDF

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 PDF

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 PDF

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 PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!