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Cerebral Cortex Advance Access published online on June 10, 2004
Cerebral Cortex, doi:10.1093/cercor/bhh096
© 2004 by Oxford University Press
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Article

Environmental Control of the Survival and Differentiation of Dentate Granule Neurons

Jeong-Ah Kim 1, Ryuta Koyama 1, Ryuji X. Yamada 1, Maki K. Yamada 1, Nobuyoshi Nishiyama 1, Norio Matsuki 1, Yuji Ikegaya 1*

1 Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan

* To whom correspondence should be addressed. E-mail: ikegaya{at}tk.air.jp.


  Abstract

Dentate granule cells (DGCs) and their microcircuits have been implicated in hippocampus-dependent memory encoding and epileptogenesis. Little is known about how the proper maturation of DGCs is determined by their intrinsic programs or external factors during development. In order to explore this, we dispersed premature DGCs on living hippocampal slices. Here we report that the survival and network formation of DGCs are supported by local cues present in the dentate gyrus ex vivo. The density of surviving DGCs was almost uniform throughout the host slices 12 h after implantation but gradually became heterogenous across substrata, with the cells engrafted onto the stratum granulosum scoring the highest rate of survival. The mossy fiber axons arising from DGCs growing on this substratum were properly guided towards CA3, whereas other misplaced DGCs exhibited heterotopic axon projection. In particular, about half of the axons originating from the hilus were misguided into the molecular layer, which resembles the supragranular mossy fiber sprouting seen in epileptic disorders. These results suggest that local environmental factors influence the cell adhesion, neurite polarization and axon guidance of DGCs.

Key Words: axon guidance, dentate gyrus, green fluorescent protein, hippocampus, mossy fiber, slice overlay assay


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