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First published online on January 18, 2002.
 Copyright © 2002 by The Physiological Society
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2001.013505v1
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Received November 7, 2001
Accepted after revision January 7, 2001

Group II metabotropic glutamate receptor activation is required for normal hippocampal mossy fibre development in the rat

Ryuta Koyama1, Maki Kobayashi Yamada1, Nobuyoshi Nishiyama1, Norio Matsuki1, and Y. Ikegaya2*

1 Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan
2 Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

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

Glutamate is a main neurotransmitter at hippocampal mossy fibre (MF) terminals. Because neurotransmitters have been proposed as regulating factors of neural network formation and neurite morphogenesis in the developing CNS, we examined the possible contribution of glutamate to MF pathfinding. Entorhino-hippocampal slices prepared from early postnatal rats were cultivated in the presence of glutamate receptor antagonists. Timm histochemical staining revealed that pharmacological blockade of metabotropic glutamate receptor (mGluR), but not of ionotropic glutamate receptors, induced abnormal outgrowth of the MFs. When slices were cultured in the presence of mGluR antagonists, DiI-labelled MF axons displayed a great degree of defasciculation, and MF-mediated EPSPs in the CA3 pyramidal cells were altered. Similar results were obtained for a selective antagonist of group II mGluR, but not of group I or III mGluR. Glutamate is, therefore, likely to regulate MF outgrowth via activation of group II mGluR. The present study may provide a novel role of glutamate in hippocampal development.




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