Questioning the depolarizing effects of GABA during early brain development.

  title={Questioning the depolarizing effects of GABA during early brain development.},
  author={Arseny S Khakhalin},
  journal={Journal of neurophysiology},
  volume={106 3},
During early brain development, γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the adult brain, has been thought to be an important source of excitatory neurotransmission. This view, however, was recently challenged by a series of studies that claim that the excitatory effect of GABA is due to non-physiological in vitro experimental conditions. In this article, we aim to summarize results that support and challenge the traditional point of view, and indicate some strong and… 

Figures from this paper

Recent progress in GABAergic excitation from mature brain

  • L. Chung
  • Biology, Psychology
    Archives of pharmacal research
  • 2012
In neural circuit activity, presumed GABAergic excitation was observed in basolateral amygdala during the study of a neuropeptide, cholecystokinin, and it may be implicated in epilepsy or anxiety in the adult brain.

GABAergic Transmission and Chloride Equilibrium Potential Are Not Modulated by Pyruvate in the Developing Optic Tectum of Xenopus laevis Tadpoles

Standard glucose-based ACSF is an appropriate extracellular media for in vitro experiments and there is a strong spatial gradient in GABA reversal potential, with immature cells adjacent to the lateral and caudal proliferative zones having more positive reversal potentials.

Emerging themes in GABAergic synapse development

Thalamic inhibitory circuits and network activity development

GABAergic Signaling Is Linked to a Hypermigratory Phenotype in Dendritic Cells Infected by Toxoplasma gondii

Evidence is provided that GABAergic signaling modulates the migratory properties of DC and that T. gondii likely makes use of this pathway for dissemination in the immune system that may be hijacked by intracellular pathogens.

Bio-functional pickles that reduce blood pressure of rats

A new type of fermentation bed composed of rice bran and white miso has been successfully developed that contains both GABA and ACE-inhibitory peptides, which is beneficial for pickle business.

Further evidence that a new type of Japanese pickles reduce the blood pressure of spontaneously hypertensive rats

It was concluded that the nukazuke could reduce the blood pressure of spontaneously hypertensive rats and the newly developed functional pickles appear to be beneficial for pickles business.



GABA Depolarizes Immature Neocortical Neurons in the Presence of the Ketone Body β-Hydroxybutyrate

In vitro, GABA depolarizes immature cells of the upper cortical plate in the presence of the ketone body βHB to support the general concept of an excitatory-to-inhibitory switch of GABA action during early development.

GABA action in immature neocortical neurons directly depends on the availability of ketone bodies

By inducing a hyperpolarizing shift in Em and modulating GABA signaling mode, KBs can efficiently control the excitability of neonatal cortical neurons.

Depolarizing Actions of GABA in Immature Neurons Depend Neither on Ketone Bodies Nor on Pyruvate

d-BHB does not alter GABA signals even at the high concentrations used by Zilberter and colleagues, whereas pyruvate requires exceedingly high nonphysiological concentrations to exert an effect, and there is no need to alter conventional glucose enriched artificial CSF to investigate GABA signals in the developing brain.

Metabolic Control of Vesicular Glutamate Transport and Release

GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations.

It is suggested that an evolutionary preserved role for excitatory GABA in immature cells provides an important mechanism in the formation of synapses and activity in neuronal networks.

Spontaneous Network Events Driven by Depolarizing GABA Action in Neonatal Hippocampal Slices are Not Attributable to Deficient Mitochondrial Energy Metabolism

The main conclusions of this work are that the inhibitory effect of l-lactate on GDPs is not mediated by mitochondrial energy metabolism, and that glucose at its standard 10 mm concentration is an adequate energy substrate for neonatal neurons in vitro.

Neuronal activity in vitro and the in vivo reality: the role of energy homeostasis.

Activity‐dependent regulation of energy metabolism by astrocytes: An update

Very recent experimental evidence as well as theoretical arguments strongly supporting the original astrocyte‐neuron lactate shuttle concept are reviewed, with new perspectives offered by the application of this concept.

Inhibition of spontaneous network activity in neonatal hippocampal slices by energy substrates is not correlated with intracellular acidification

J. Neurochem. (2011) 116, 316–321.