Odor-Induced, Activity-Dependent Transneuronal Gene Induction In Vitro: Mediation by NMDA Receptors

• Published in: The Journal of neuroscience Vol. 19; no. 4; pp. 1359 - 1370
• Main Authors: Puche, A. C, Shipley, M. T
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 15-02-1999
• Subjects: Animals; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Cell Count; Cells, Cultured; Coculture Techniques; Excitatory Amino Acid Agonists - pharmacology; Juxtaglomerular Apparatus - cytology; Juxtaglomerular Apparatus - metabolism; Neurons - physiology; Odorants; Olfactory Bulb - cytology; Olfactory Bulb - metabolism; Organ Culture Techniques; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - physiology; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.19-04-01359.1999

Expression of tyrosine hydroxylase (TH) by juxtaglomerular (JG) neurons of the olfactory bulb (OB) requires innervation of the bulb by olfactory receptor neurons (ORNs). ORN lesion selectively downregulates TH in JG neurons. In reversible odor deprivation, TH expression is downregulated as the naris is closed and then upregulated upon naris reopening. The mechanism or mechanisms regulating this dependence are unknown. TH expression could be regulated by trophic factor release and/or synaptic activity from ORN terminals. We investigated TH expression in cocultures of dissociated postnatal rat OB cells and embryonic olfactory neuroepithelium (OE) slice explants. TH-positive neurons in control dissociated OB cell cultures alone comprise only a small fraction of the total population of cells present in the culture. However, when OE slice explants are cocultured with dispersed OB cells, there is a mean 2.4-fold increase in the number of TH-positive neurons. ORNs in vivo use glutamate as a neurotransmitter. Broad spectrum excitatory amino acid antagonists (kyurenic acid) or selective antagonists of the NMDA receptor (APV) both prevent induction of TH expression in OE-OB cocultures. Furthermore, pulse application of NMDA stimulates TH expression in OB neurons in the absence of OE. In vitro, OB TH neurons express NMDA receptors, suggesting that NMDA stimulation is acting directly on TH neurons. Exposure of OE explants to natural odorants results in upregulation of TH, presumably through increased ORN activity, which could be blocked by APV. These findings indicate that odorant-stimulated glutamate release by ORN terminals regulates TH expression via NMDA receptors on JG dopaminergic neurons.