» Articles » PMID: 22529813

Excitatory GABA: How a Correct Observation May Turn Out to Be an Experimental Artifact

Overview
Journal Front Pharmacol
Date 2012 Apr 25
PMID 22529813
Citations 38
Authors
Affiliations
Soon will be listed here.
Abstract

The concept of the excitatory action of GABA during early development is based on data obtained mainly in brain slice recordings. However, in vivo measurements as well as observations made in intact hippocampal preparations indicate that GABA is in fact inhibitory in rodents at early neonatal stages. The apparent excitatory action of GABA seems to stem from cellular injury due to the slicing procedure, which leads to accumulation of intracellular Cl(-) in injured neurons. This procedural artifact was shown to be attenuated through various manipulations such as addition of energy substrates more relevant to the in vivo situation. These observations question the very concept of excitatory GABA in immature neuronal networks.

Citing Articles

Chemogenetics with PSAM-GlyR decreases excitability and epileptiform activity in epileptic hippocampus.

Gonzalez-Ramos A, Berglind F, Kudlacek J, Rocha E, Melin E, Sebastiao A Gene Ther. 2024; .

PMID: 39455855 DOI: 10.1038/s41434-024-00493-7.


How Staying Negative Is Good for the (Adult) Brain: Maintaining Chloride Homeostasis and the GABA-Shift in Neurological Disorders.

Hui K, Chater T, Goda Y, Tanaka M Front Mol Neurosci. 2022; 15:893111.

PMID: 35875665 PMC: 9305173. DOI: 10.3389/fnmol.2022.893111.


Striatal Chloride Dysregulation and Impaired GABAergic Signaling Due to Cation-Chloride Cotransporter Dysfunction in Huntington's Disease.

Serranilla M, Woodin M Front Cell Neurosci. 2022; 15:817013.

PMID: 35095429 PMC: 8795088. DOI: 10.3389/fncel.2021.817013.


Human Stem Cell-Derived GABAergic Interneurons Establish Efferent Synapses onto Host Neurons in Rat Epileptic Hippocampus and Inhibit Spontaneous Recurrent Seizures.

Waloschkova E, Gonzalez-Ramos A, Mikroulis A, Kudlacek J, Andersson M, Ledri M Int J Mol Sci. 2021; 22(24).

PMID: 34948040 PMC: 8705828. DOI: 10.3390/ijms222413243.


Sustainable Brain Activity and no End in Sight-What's in It for Status Epilepticus?.

Gross C Epilepsy Curr. 2020; 20(2):113-115.

PMID: 32313508 PMC: 7160873. DOI: 10.1177/1535759720901509.


References
1.
Szabadics J, Varga C, Molnar G, Olah S, Barzo P, Tamas G . Excitatory effect of GABAergic axo-axonic cells in cortical microcircuits. Science. 2006; 311(5758):233-5. DOI: 10.1126/science.1121325. View

2.
Ben-Ari Y, Khazipov R, Leinekugel X, Caillard O, Gaiarsa J . GABAA, NMDA and AMPA receptors: a developmentally regulated 'ménage à trois'. Trends Neurosci. 1997; 20(11):523-9. DOI: 10.1016/s0166-2236(97)01147-8. View

3.
Garthwaite J, Woodhams P, Collins M, Balazs R . On the preparation of brain slices: morphology and cyclic nucleotides. Brain Res. 1979; 173(2):373-7. DOI: 10.1016/0006-8993(79)90641-3. View

4.
Ivanov A, Mukhtarov M, Bregestovski P, Zilberter Y . Lactate Effectively Covers Energy Demands during Neuronal Network Activity in Neonatal Hippocampal Slices. Front Neuroenergetics. 2011; 3:2. PMC: 3092068. DOI: 10.3389/fnene.2011.00002. View

5.
Benjamin A, Verjee Z . Control of aerobic glycolysis in the brain in vitro. Neurochem Res. 1980; 5(9):921-34. DOI: 10.1007/BF00966133. View