Puche A C, Shipley M T
Department of Anatomy and Neurobiology, Program in Neuroscience, School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA.
J Neurosci. 1999 Feb 15;19(4):1359-70. 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.
嗅球(OB)的球旁(JG)神经元中酪氨酸羟化酶(TH)的表达需要嗅觉受体神经元(ORN)对嗅球的支配。ORN损伤会选择性地下调JG神经元中的TH。在可逆性气味剥夺中,随着鼻孔关闭,TH表达下调,而在鼻孔重新打开时则上调。调节这种依赖性的机制尚不清楚。TH表达可能受营养因子释放和/或ORN终末的突触活动调节。我们研究了新生大鼠OB解离细胞与胚胎嗅神经上皮(OE)切片外植体共培养物中的TH表达。仅在对照解离OB细胞培养物中的TH阳性神经元仅占培养物中细胞总数的一小部分。然而,当OE切片外植体与分散的OB细胞共培养时,TH阳性神经元的数量平均增加2.4倍。体内的ORN使用谷氨酸作为神经递质。广谱兴奋性氨基酸拮抗剂(犬尿氨酸)或NMDA受体的选择性拮抗剂(APV)均可阻止OE-OB共培养物中TH表达的诱导。此外,在没有OE的情况下,脉冲施加NMDA可刺激OB神经元中TH的表达。在体外,OB的TH神经元表达NMDA受体,这表明NMDA刺激直接作用于TH神经元。将OE外植体暴露于天然气味剂会导致TH上调,推测是通过增加ORN活性,而这可被APV阻断。这些发现表明,ORN终末的气味剂刺激的谷氨酸释放通过JG多巴胺能神经元上的NMDA受体调节TH表达。