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The Journal of Neuroscience, May 9, 2007, 27(19):5224-5235; doi:10.1523/JNEUROSCI.5169-06.2007

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Development/Plasticity/Repair
Excitatory GABA Action Is Essential for Morphological Maturation of Cortical Neurons In Vivo

Laura Cancedda, * Hubert Fiumelli, * Karen Chen, and Mu-ming Poo

Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, California 94720-3200

Correspondence should be addressed to Mu-ming Poo at the above address. Email: mpoo{at}berkeley.edu

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 GABAA 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.

Key words: KCC2; development; radial migration; Kir2.1; in utero electroporation; gramicidin perforated-patch


Received Nov. 29, 2006; revised March 7, 2007; accepted March 26, 2007.

Correspondence should be addressed to Mu-ming Poo at the above address. Email: mpoo{at}berkeley.edu


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