Excitatory GABA Action Is Essential for Morphological Maturation of Cortical Neurons In Vivo

By Laura Cancedda, H. Fiumelli, Karen S. Chen, Mu-Ming Poo. 2007

407 citations recorded by the source corpus.

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.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. Fred H. Gage
2. Hongjun Song
3. Guo-li Ming
4. S. Ge
5. Kurt Sailor
6. D. C. Lie
7. M. Saxe
8. James Bradley Aimone

In Molecular Biology

1. Hongjun Song
2. Guo-li Ming
3. Fred H. Gage
4. D. C. Lie
5. C. Rivera
6. M. S. Airaksinen
7. Kurt Sailor
8. Kai Kaila

Citations in the corpus

• Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “Is there a similar reserved pool of neural stem cells in the adult CNS?Do they transit through a resident neural precursor stage to give rise to neurons and glia? While still under debate, the ependymal cells lining the ventricles have been proposed as a reservoir of neural stem cells that are recru”
• Synaptic integration and plasticity of new neurons in the adult hippocampus (2008, background): “A similar role of GABA has been demonstrated in the development of mouse embryonic cortical neurons (Cancedda et al. 2007; Wang & Kriegstein, 2008) and Xenopus tectum neurons (Akerman & Cline, 2006) in vivo.”
• Raising cytosolic Cl− in cerebellar granule cells affects their excitability and vestibulo‐ocular learning (2012, neutral): “…[Cl (cid:2) ] in tectal neurons of Xenopus by Kcc2 expression blocks their AMPA-R mediated retinotectal transmission (Akerman and Cline, 2006), and premature expression of Kcc2 in rat ventricular progenitors and cortical neurons impaired morphological maturation (Cancedda et al , 2007).”
• Cation-chloride cotransporters and neuronal function. (2009, background): “On the other hand, using in utero electroporation to overexpress KCC2 in proliferating neurons, Cancedda et al. (2007) found that while neuronal migration was not affected (but see Heck et al., 2007), morphological maturation was markedly impaired in immature neurons that were devoid of…”
• GABA-CREB signalling regulates maturation and survival of newly generated neurons in the adult hippocampus (2009, background): “The dependency of neuronal maturation on GABA-induced membrane depolarization is not confined to adult neurogenesis but is a recurring theme throughout CNS development (Ben-Ari, 2002; Cancedda et al., 2007).”