The rostral migratory stream generates hippocampal CA1 pyramidal-like neurons in a novel organotypic slice co-culture model.

Ilyas Singec,Michael Frotscher,Imre Vida,Rolf Knoth

doi:10.1242/bio.012096

Abstract

ABSTRACTThe mouse subventricular zone (SVZ) generates large numbers of neuroblasts, which migrate in a distinct pathway, the rostral migratory stream (RMS), and replace specific interneurons in the olfactory bulb (OB). Here, we introduce an organotypic slice culture model that directly connects the RMS to the hippocampus as a new destination. RMS neuroblasts widely populate the hippocampus and undergo cellular differentiation. We demonstrate that RMS cells give rise to various neuronal subtypes and, surprisingly, to CA1 pyramidal neurons. Pyramidal neurons are typically generated before birth and are lost in various neurological disorders. Hence, this unique slice culture model enables us to investigate their postnatal genesis under defined in vitro conditions from the RMS, an unanticipated source for hippocampal pyramidal neurons.

Highlights

Neural stem cells (NSCs) of the subventricular zone (SVZ) reside in the lateral walls of the lateral ventricles and the dentate gyrus (DG) of the hippocampus and generate new neurons throughout rodent life (Lledo et al, 2008)
We found that rostral migratory stream (RMS) cells can integrate into the hippocampal CA1 region and properly differentiate into pyramidal neuron-like cells. These findings suggest the existence of molecular cues and environmental signals that can reprogram the cellular fate of olfactory neuroblasts into appropriate hippocampal principal neurons
Organotypic slice cultures derived from different brain regions have been used in previous studies and enable important experiments otherwise not feasible in the intact brain or primary cultures containing dissociated cells (Gähwiler et al, 1997; De Marchis et al, 2001; Tanvig et al, 2009)

Summary

Introduction

Neural stem cells (NSCs) of the SVZ reside in the lateral walls of the lateral ventricles and the dentate gyrus (DG) of the hippocampus and generate new neurons throughout rodent life (Lledo et al, 2008). To test the cellular plasticity of the RMS under organotypic conditions, we established a novel slice co-culture model by surgically removing the OB and connecting the RMS directly to the hippocampus as a new destination. We demonstrate that large numbers of RMS cells populate the different hippocampal regions and differentiate into various neuronal cell types.

Results

Conclusion