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Cerebral Cortex 1995; 5:64-78
© Oxford University Press 1995

research-article

Basic Fibroblast Growth Factor Increases the Number of Excitatory Neurons Containing Glutamate in the Cerebral Cortex

Flora M. Vaccarino1,, Michael L. Schwartz2, Dennis Hartigan1 and James F. Leckman1

1 Child Study Center, Yale University New Haven, Connecticut 06510, 2 Section of Neurobiology, Yale University New Haven, Connecticut 06510

Correspondence should be addressed to: F. M. Vaccarino, Child Study Center, Yale University, P.O. Box 3333, New Haven, CT 06510

Stem cells isolated from the ventricular zone of embryonic day 12.5 rat telencephalon progressively proliferate and differentiate in vitro into three major classes of amino acid-containing neurons, glutamate, aspartate, and GABA. We quantitatively examined the effect of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) on amino acid-containing neurons. bFGF caused a threefold increase in glutamate-containing neurons, while the number of GABA- and aspartatecontaining neurons was not significantly changed. In contrast, NGF did not alter the number of amino acid-containing neurons. The ratio of glutamate- to GABA-containing neurons in untreated or NGF-treated cultures was 0.6:1. In the bFGF-treated cultures, this ratio was 1.4:1, which closely approximates the ratio in the cerebral cortex in vivo. Treatment with antisense oligonucleotidos targeted to bFGF mRNA provoked a 50% decrease in the number of glutamate-containing neurons but had no significant effect on the GABA-containing neurons. Thus, diffusible factors such as bFGF may play an important role in determining the relative proportion of excitatory versus inhibitory neurons in the cerebral cortex by selectively regulating the proliferation of stem cells committed to different neurotransmitter phenotypes.


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