An ion transport-independent role for the cation-chloride cotransporter KCC2 in dendritic spinogenesis in vivo

Article Article scientifique Article An ion transport-independent role for the cation-chloride cotransporter KCC2 in dendritic spinogenesis in vivo eng 2013 author Fiumelli Hubert author Briner Adrian 653735 author Puskarjov Martin author Blaesse Peter author Belem Bebyanda John Thierry 689496 author Dayer Alexandre 84495 author Kaila Kai author Martin Jean-Luc 31411 author Vutskits Laszlo 0000-0001-8752-9588 109383 378-388 10.1093/cercor/bhs027 22345354 1047-3211 The neuron-specific K-Cl cotransporter, KCC2, is highly expressed in the vicinity of excitatory synapses in pyramidal neurons, and recent in vitro data suggest that this protein plays a role in the development of dendritic spines. The in vivo relevance of these observations is, however, unknown. Using in utero electroporation combined with post hoc iontophoretic injection of Lucifer Yellow, we show that premature expression of KCC2 induces a highly significant and permanent increase in dendritic spine density of layer 2/3 pyramidal neurons in the somatosensory cortex. Whole-cell recordings revealed that this increased spine density is correlated with an enhanced spontaneous excitatory activity in KCC2-transfected neurons. Precocious expression of the N-terminal deleted form of KCC2, which lacks the chloride transporter function, also increased spine density. In contrast, no effect on spine density was observed following in utero electroporation of a point mutant of KCC2 (KCC2-C568A) where both the cotransporter function and the interaction with the cytoskeleton are disrupted. Transfection of the C-terminal domain of KCC2, a region involved in the interaction with the dendritic cytoskeleton, also increased spine density. Collectively, these results demonstrate a role for KCC2 in excitatory synaptogenesis in vivo through a mechanism that is independent of its ion transport function. Animals Dendritic Spines/metabolism Electroporation Immunohistochemistry Neurogenesis/physiology Patch-Clamp Techniques Pyramidal Cells/growth & development/metabolism Rats Rats, Wistar Somatosensory Cortex/growth & development/metabolism Symporters/metabolism Transfection Dewey 616.8 Dewey 617 53 Département de neurosciences fondamentales 21A 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 false 543 Anesthésie et neurosciences 883 535 Groupe Dayer Alexandre (Formation du circuit cortical) 875 Cerebral cortex 23 2 f2ae8f32-68c3-403e-ae77-aa9b342feb2b Article (Published version) Restricted Cereb. Cortex-2013-Fiumelli-378-88.pdf 3233557 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences

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An ion transport-independent role for the cation-chloride cotransporter KCC2 in dendritic spinogenesis in vivo	Cerebral cortex			2013	814	6

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Martin, Jean-Luc