GABA Neurotransmission: An Overview

Schousboe, Arne; Waagepetersen, Helle S.

doi:10.1007/978-0-387-30382-6_9

Cited by 8 publications

(5 citation statements)

References 100 publications

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“…In the synaptic cleft, GABA binds its receptors at the postsynaptic density. Unbound GABA is either recycled to the presynaptic terminal by one of various GABA transporters or transported to the glial cells where it is metabolized to glutamate [7,29].…”

Section: The Gaba a Receptormentioning

confidence: 99%

Involvement and Therapeutic Potential of the GABAergic System in the Fragile X Syndrome

Heulens

D’Hulst²,

Braat³

et al. 2010

The Scientific World JOURNAL

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Many drugs have been developed that are able to modulate the GABAergic system, which is involved in anxiety, depression, epilepsy, insomnia, and learning and memory. The recent observation that the GABAA receptor is underexpressed in the fragile X syndrome, an inherited mental retardation disorder, therefore raised hopes for targeted therapy of the disorder. This review summarizes the lines of evidence that demonstrate a malfunction of the GABAergic system. The GABAergic system clearly emerges as an attractive target for therapy of the fragile X syndrome, and thus provides an excellent example of how genetic research can lead to unique opportunities for treatment.

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Section: The Gaba a Receptormentioning

confidence: 99%

Involvement and Therapeutic Potential of the GABAergic System in the Fragile X Syndrome

Heulens

D’Hulst²,

Braat³

et al. 2010

The Scientific World JOURNAL

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“…Due to the fact that these amino acids were present in much higher concentrations than the classical neurotransmitters acetylcholine and the monoamines it took several years until it was generally accepted that these two amino acids are not just metabolites but they constitute the quantitatively most important neurotransmitters in the central nervous system [see reviews by Ref. (5) and (6)].…”

Section: Introductionmentioning

confidence: 99%

Astrocytic Control of Biosynthesis and Turnover of the Neurotransmitters Glutamate and GABA

Schousboe¹,

Bak²,

2013

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Glutamate and GABA are the quantitatively major neurotransmitters in the brain mediating excitatory and inhibitory signaling, respectively. These amino acids are metabolically interrelated and at the same time they are tightly coupled to the intermediary metabolism including energy homeostasis. Astrocytes play a pivotal role in the maintenance of the neurotransmitter pools of glutamate and GABA since only these cells express pyruvate carboxylase, the enzyme required for de novo synthesis of the two amino acids. Such de novo synthesis is obligatory to compensate for catabolism of glutamate and GABA related to oxidative metabolism when the amino acids are used as energy substrates. This, in turn, is influenced by the extent to which the cycling of the amino acids between neurons and astrocytes may occur. This cycling is brought about by the glutamate/GABA – glutamine cycle the operation of which involves the enzymes glutamine synthetase (GS) and phosphate-activated glutaminase together with the plasma membrane transporters for glutamate, GABA, and glutamine. The distribution of these proteins between neurons and astrocytes determines the efficacy of the cycle and it is of particular importance that GS is exclusively expressed in astrocytes. It should be kept in mind that the operation of the cycle is associated with movement of ammonia nitrogen between the two cell types and different mechanisms which can mediate this have been proposed. This review is intended to delineate the above mentioned processes and to discuss quantitatively their relative importance in the homeostatic mechanisms responsible for the maintenance of optimal conditions for the respective neurotransmission processes to operate.

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“…To model the uptake from ECS by astrocyte through EAAT1 and EAAT2, we simply replace A up by the total membrane area of the astrocyte (A up e→g ) in Eq. (9). Similarly, the neuronal uptake from ECS is modeled by using the total membrane area of the neuron (A up e→n ).…”

Section: Glutamate Release and Diffusionmentioning

confidence: 99%

“…Signal integration in the brain is determined by the amplitude and kinetics of synaptic responses [1,2], which in turn are controlled by the spatiotemporal dynamics of neurotransmitter concentrations in the synaptic cleft [3,4,5]. Among many, glutamate and gamaaminobutyric acide (GABA) are the major excitatory and inhibitory neurotransmitters, and are thereby involved in most aspects of normal brain function including cognition, memory, and learning, and many neuronal disorders [6,7,8,9,10,11]. A tight control of both glutamate and GABA in the synaptic cleft and extracellular space (ECS) is therefore crucial for avoiding abnormal neuronal activity [7,12,13,14].…”

Section: Introductionmentioning

confidence: 99%

“…In the absence of extracellular metabolism, cellular uptake maintains low levels of glutamate and GABA concentrations in the cleft and ECS to avoid excitotoxicity or overinhibition in the brain [15,9,7,16,17]. It has been clear for almost fifty years now that both neurons and astrocytes express different types of transporters to buffer glutamate and GABA from the synaptic cleft and ECS and restore their intracellular pools [7,18,10,14,16,19,20,21].…”

Section: Introductionmentioning

confidence: 99%

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The role of transporters and synaptic cleft morphology in glutamate and GABA homeostasis and their effect on neuronal function

Ullah

2019

Preprint

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The spatiotemporal dynamics of glutamate and gama-aminobutyric acide (GABA) in the synaptic cleft plays a key role in the signal integration in the brain. Since there is no extracellular metabolism of glutamate and GABA, cellular uptake through transporters and diffusion to extracellular space (ECS) regulates the concentration of both neurotransmitters in the cleft. We use the most up to date information about the transporters and synaptic cleft to model the homeostasis of both glutamate and GABA. We show that the models can be used to investigate the role played by different isoforms of transporters, uptake by different neuronal compartments or glia cells, and key parameters determining the morphology of synaptic cleft in the neurotransmitter concentration in the cleft and ECS, and how they shape synaptic responses through postsynaptic receptors. We demonstrate the utility of our models by application to simple neuronal networks and showing that varying the neurotransmitter uptake capacity and synaptic cleft parameters within experimentally observed range can lead to significant changes in neuronal behavior such as the transition of the network between gamma and beta rhythms. The modular form of the models allows easy extension in the future and integration with other computational models of normal and pathological neuronal functions.

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GABA Neurotransmission: An Overview

Cited by 8 publications

References 100 publications

Involvement and Therapeutic Potential of the GABAergic System in the Fragile X Syndrome

Involvement and Therapeutic Potential of the GABAergic System in the Fragile X Syndrome

Astrocytic Control of Biosynthesis and Turnover of the Neurotransmitters Glutamate and GABA

The role of transporters and synaptic cleft morphology in glutamate and GABA homeostasis and their effect on neuronal function

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