GABAB receptor expression and function in olfactory receptor neuron axon growth.
Neurotransmitters have been implicated in regulating growth cone motility and guidance in the developing nervous system. Anatomical and electrophysiological studies show the presence of functional GABAB receptors on adult olfactory receptor neuron (ORN) nerve terminals. Using antisera against the GABAB R1a/b receptor isoforms we show that developing mouse olfactory receptor neurons express GABAB receptors from embryonic day 14 through to adulthood. GABAB receptors are present on axon growth cones from both dissociated ORNs and olfactory epithelial explants. Neurons in the olfactory bulb begin to express glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA, from E16 through to adulthood. When dissociated ORNs were cultured in the presence of the GABAB receptor agonists, baclofen or SKF97541, neurite outgrowth was significantly reduced. Concurrent treatment of the neurons with baclofen and the GABAB receptor antagonist CGP54626 prevented the inhibitory effects of baclofen on ORN neurite outgrowth. These results show that growing ORN axons express GABAB receptors and are sensitive to the effects of GABAB receptor activation. Thus, ORNs in vivo may detect GABA release from juxtaglomerular cells as they enter the glomerular layer and use this as a signal to limit their outgrowth and find synaptic targets in regeneration and development.
Priest
Catherine A
CA
Department of Anatomy and Neurobiology, Program in Neuroscience, The University of Maryland School of Medicine, Room 222, 685 West Baltimore Street, Baltimore, Maryland 21201, USA.
Puche
Adam C
AC
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D001418:Baclofen / Q000494:pharmacology; D002478:Cells, Cultured; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D005786:Gene Expression Regulation / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D020439:Growth Cones / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009830:Olfactory Bulb / Q000166:cytology / Q000196:embryology / Q000502:physiology; D009831:Olfactory Mucosa / Q000166:cytology*; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011247:Pregnancy; D018080:Receptors, GABA-B / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C068457:3-aminopropyl(methyl)phosphinic acid; C107353:CGP 54626; D005968:Glutamate Decarboxylase; D001418:Baclofen