1. Excitatory GABA action is essential for morphological maturation of cortical neurons in vivo.
- Author
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Cancedda L, Fiumelli H, Chen K, and Poo MM
- Subjects
- Animals, Animals, Newborn, Bacterial Proteins genetics, Cell Communication physiology, Cell Membrane genetics, Cell Membrane metabolism, Cell Movement drug effects, Cell Movement genetics, Cerebral Cortex cytology, GABA Antagonists pharmacology, GABA-A Receptor Antagonists, Green Fluorescent Proteins genetics, Luminescent Proteins genetics, Membrane Potentials genetics, Neurons cytology, Organ Culture Techniques, Potassium Channels, Inwardly Rectifying genetics, Potassium Channels, Inwardly Rectifying metabolism, Rats, Rats, Sprague-Dawley, Receptors, GABA-A metabolism, Stem Cells metabolism, Symporters genetics, Symporters metabolism, Synaptic Transmission drug effects, gamma-Aminobutyric Acid pharmacology, K Cl- Cotransporters, Cell Differentiation physiology, Cerebral Cortex embryology, Cerebral Cortex growth & development, Neurons metabolism, Synaptic Transmission genetics, gamma-Aminobutyric Acid metabolism
- Abstract
GABA exerts excitatory actions on embryonic and neonatal cortical neurons, but the in vivo function of this GABA excitation is essentially unknown. Using in utero electroporation, we eliminated the excitatory action of GABA in a subpopulation of rat ventricular progenitors and cortical neurons derived from these progenitors by premature expression of the Cl- transporter KCC2, as confirmed by the changes in the reversal potential of GABA-induced currents and the resting membrane potential after GABA(A) receptor blockade. We found that radial migration to layer II/III of the somatosensory cortex of neurons derived from the transfected progenitors was not significantly affected, but their morphological maturation was markedly impaired. Furthermore, reducing neuronal excitability of cortical neurons in vivo by overexpressing an inward-rectifying K+ channel, which lowered the resting membrane potential, mimicked the effect of premature KCC2 expression. Thus, membrane depolarization caused by early GABA excitation is critical for morphological maturation of neonatal cortical neurons in vivo.
- Published
- 2007
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