Cajal-Retzius cells fail to trigger the developmental expression of the Cl- extruding co-transporter KCC2.
Cajal-Retzius (CR) cells are transient neurons of the developing cerebral cortex that play a pivotal role in the lamination and construction of neural circuits. One physiological feature of CR cells is the failure to switch GABAergic transmission from excitation to inhibition. To examine the mechanisms underlying the persistence of the depolarizing action of GABA we analyzed the mRNA expression of the K+/Cl- co-transporter type 2 (KCC2) in mouse CR by in situ hybridization. During the second postnatal week, the developmentally regulated expression of KCC2 reached adult levels in most neurons of the cerebral cortex. Double labeling with the CR-cell marker calretinin and KCC2 in situ hybridization showed that CR cells were consistently devoid of KCC2 expression in several cortical areas such as neocortex and hippocampus. Since most cortical calretinin- and calbindin-containing non-CR neurons did express KCC2 mRNA, we conclude that CR cells specifically fail to trigger the developmental expression of the K+/Cl- co-transporter KCC2. These results suggest that absence of KCC2 preserves the depolarizing action of GABA in CR cells and support the notion that KCC2 is a key factor controlling Cl- homeostasis and preventing hyperexcitability.
Pozas
Esther
E
Department of Brain Ischemia and Neurodegeneration, Institute for Biomedical Research of Barcelona (IIBB), CSIC-IDIBAPS, Spain.
Paco
Sonia
S
Soriano
Eduardo
E
Aguado
Fernando
F
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D001921:Brain / Q000196:embryology / Q000254:growth & development* / Q000502:physiology*; D064032:Calbindin 2; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006624:Hippocampus / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008815:Mice, Inbred Strains; D019579:Neocortex / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010784:Photomicrography; D017966:Pyramidal Cells / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D027981:Symporters / Q000235:genetics* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000096922:K Cl- Cotransporters
D064032:Calbindin 2; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters; C576511:Calb2 protein, mouse