The KCC2 Influence on Neuronal Migration in Ferret Neocortex
Abstract
KCC2 is a brain specific potassium-chloride cotransporter that affects development of the cerebral cortex, including aspects of neuronal migration and cellular maturation and differentiation. KCC2 also modulates chloride homeostasis by influencing the switch of GABA from depolarizing in young neurons to hyperpolarizing in mature neurons. This switch in polarity is believed to contribute to the guidance cues thatmodulate termination of neuronal migration. The expression of KCC2 during migration of interneurons correlates with the ability of these cells to respond to GABA as a stop signal, suggesting that KCC2 might act as a switch controlling GABA from acting in a motogenic capacity to becoming a stop signal in migrating neurons. Therefore, manipulation of KCC2 expression or its activity early in development can affect variousaspects of migrating neurons, including the speed. We earlier developed a model of impaired cortical development by injecting methylazoxymethanol acetate (MAM) into pregnant ferrets during mid-cortical gestation, which briefly interferes with neuronal production, disrupts neuronal migration, and results in increased production of KCC2. We first describe the expression pattern, regional distribution and cellular colocalization of KCC2 with other neuronal markers in ferret neocortex in normal kits and those treated with MAM (Chapter 2). Next we study the effect of KCC2 downregulation on the migration of neurons away from the ganglionic eminence (GE) and into the neocortex at postnatal day 0 (P0) in ferret organotypic slice cultures (Chapter 3). In Chapter 2 we show a shift in KCC2 expression during development from being strong in the subplate at P0, repositioning into a subtle laminar pattern at P7-P14 and becoming homogeneous at P35. In the immature cortex, the KCC2 immunoreactivity was clearly located in migrating neurons and occurred in the cell membrane and cell processes and extended into the cytoplasm.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 11, 2017
- Accession Number
- AD1128233
Entities
People
- Francis T. Djankpa
Organizations
- Uniformed Services University of the Health Sciences