Excitatory GABA action is essential for morphological maturation of cortical neurons in vivo.
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.
Cancedda
Laura
L
Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, California 94720-3200, USA.
Fiumelli
Hubert
H
Chen
Karen
K
Poo
Mu-ming
MM
D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D049452:Green Fluorescent Proteins / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D008564:Membrane Potentials / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009924:Organ Culture Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology; D000096922:K Cl- Cotransporters
D001426:Bacterial Proteins; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D024661:Potassium Channels, Inwardly Rectifying; D011963:Receptors, GABA-A; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters; C489461:Kir2.1 channel; C485184:enhanced green fluorescent protein; C054562:yellow fluorescent protein, Bacteria