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Received May 10, 2005
Revised June 2, 2005
Accepted after revision June 10, 2005
1 INMED/INSERM
2 Zentrum fuer Molekulare Neurobiologie Universitaet Hamburg
* To whom correspondence should be addressed. E-mail: medina{at}inmed.univ-mrs.fr.
The development of GABAergic synapses is associated with an excitatory to inhibitory shift of the actions of GABA because of a reduction of [Cl-]i . This is due to a delayed postnatal expression of the K+, Cl- cotransporter KCC2 , which has low levels at birth and peaks during the first few postnatal weeks. Whether the expression of the cotransporter and the excitatory to inhibitory shift have other consequences on the operation of GABA receptors and synapses is not yet known. We have now expressed KCC2 in immature neurons at an early developmental stage and determined the consequences on the formation of GABA and glutamate synapses. We report that early expression of the cotransporter selectively enhances GABAergic synapses: there is a significant increase of the density of GABA receptors and synapses and an increase of the frequency of GABAergic miniature postsynaptic currents. The density of glutamate synapses and frequency of AMPA miniature postsynaptic currents are not affected. We conclude that the expression of KCC2 and the reduction of [Cl-]i play a critical role in the construction of GABAergic networks that extends beyond the excitatory to inhibitory shift of the actions of GABA.
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