Refuting the challenges of the developmental shift of polarity of GABA actions: GABA more exciting than ever!

Yehezkel Ben-Ari,Atsuo Fukuda,Angelique Bordey,Peter Wenner,Anthony N Van Den Pol,Heiko J Luhmann,Jean-Luc Gaiarsa,Evelyne Sernagor,Laura Cancedda,Claudio Rivera,Melanie A Woodin,Laurent Vinay,Pascal Legendre,Enrico Cherubini

doi:10.3389/fncel.2012.00035

Abstract

During brain development, there is a progressive reduction of intracellular chloride associated with a shift in GABA polarity: GABA depolarizes and occasionally excites immature neurons, subsequently hyperpolarizing them at later stages of development. This sequence, which has been observed in a wide range of animal species, brain structures and preparations, is thought to play an important role in activity-dependent formation and modulation of functional circuits. This sequence has also been considerably reinforced recently with new data pointing to an evolutionary preserved rule. In a recent “Hypothesis and Theory Article,” the excitatory action of GABA in early brain development is suggested to be “an experimental artefact” (Bregestovski and Bernard, 2012). The authors suggest that the excitatory action of GABA is due to an inadequate/insufficient energy supply in glucose-perfused slices and/or to the damage produced by the slicing procedure. However, these observations have been repeatedly contradicted by many groups and are inconsistent with a large body of evidence including the fact that the developmental shift is neither restricted to slices nor to rodents. We summarize the overwhelming evidence in support of both excitatory GABA during development, and the implications this has in developmental neurobiology.

Highlights

We summarize the overwhelming evidence in support of both excitatory GABA during development, and the implications this has in developmental neurobiology
The overwhelming convergence of observations made in a wide range of animal species and preparations confirm the developmental sequence of the polarity of GABA as a genuine fundamental feature of developmental neurobiology
This is another illustration of the developmental sequences that occur with all voltage and transmitter gated currents reflecting the major differences between the developing and adult brain: the developing brain is not a small adult brain

Summary

CELLULAR NEUROSCIENCE

There is a progressive reduction of intracellular chloride associated with a shift in GABA polarity: GABA depolarizes and occasionally excites immature neurons, subsequently hyperpolarizing them at later stages of development This sequence, which has been observed in a wide range of animal species, brain structures and preparations, is thought to play an important role in activity-dependent formation and modulation of functional circuits. It is quite difficult to understand why surface neurons would exhibit depolarizing GABAergic responses and alter spontaneous network activity between P5–P14 and not earlier or later This is inconsistent with the observation that during the 2nd postnatal week, GABA exerts hyperpolarizing actions and the GDPs are replaced by Large Hyperpolarizing Potentials at that stage (Ben-Ari et al, 1989). Radial migration requires high intracellular Cl− as applications of GABA receptor antagonists to slice cultures or subdural to neonatal rats accelerated radial migration (Heck et al, 2007; Manent and Represa, 2007)

CONCLUSIONS

Efficacy and stability of quantal