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The Journal of Neuroscience, August 11, 2004, 24(32):7085-7095; doi:10.1523/JNEUROSCI.0349-04.2004

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Development/Plasticity/Repair
The Neurotransmitter Glutamate Reduces Axonal Responsiveness to Multiple Repellents through the Activation of Metabotropic Glutamate Receptor 1

Thomas A. Kreibich, * Sreekanth H. Chalasani, * and Jonathan A. Raper

Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Glutamate is the major excitatory neurotransmitter in the mammalian CNS. Here, we propose a new role for this neurotransmitter in the developing nervous system. We show that glutamate or the metabotropic class I agonist S-3,5-dihydroxyphenyl glycine, acting through the metabotropic glutamate receptor 1 (mGluR1), can reduce the activity of multiple axonal repellents in vitro. This effect is mediated by a pertussis toxin-sensitive activation of protein kinase A and the subsequent inactivation of Rho. This signaling pathway appears to be identical to the one we described previously for stromal derived factor-1-induced reduction of axonal repellent activities. Activation of mGluR1 can also promote increased survival of embryonic retinal ganglion cells in culture. We propose that neurotransmitter-induced modulation of repellent strength provides a novel mechanism by which activity can influence neuronal morphology.

Key words: axon guidance; growth cone; metabotropic glutamate receptor; slit-2; semaphorin 3A; semaphorin 3C; cAMP; survival; neurotrophic

Received Jan 30, 2004; revised June 18, 2004; accepted June 20, 2004.




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