Nitric oxide mediates the formation of synaptic connections in developing and regenerating olfactory receptor neurons.
Nitric oxide (NO) is a diffusible free radical that functions as a second messenger and neurotransmitter. NO synthase (NOS) is highly and transiently expressed in neurons of the developing olfactory epithelium during migration and establishment of primary synapses in the olfactory bulb. NOS is first expressed at E11 in cells of the presumptive nervous layer of the olfactory placode. NOS immunoreactivity persists in the descendants of these cells that differentiate into embryonic olfactory receptor neurons (ORNs). Olfactory NOS expression in the ORN and in its afferents rapidly declines after birth and is undetectable by P7. Following bulbectomy, NOS expression is rapidly induced in the regenerating ORN and is particularly enriched in their outgrowing axons. Immunoblot and Northern blot analyses similarly demonstrate an induction of NOS protein and mRNA expression, respectively, the highest levels of which coincide with peaks of ORN regeneration. These data argue against a role for NO in odorant-sensitive signal transduction, but suggest a prominent function for NO in activity-dependent establishment of connections in both developing and regenerating olfactory neurons.
Roskams
A J
AJ
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Bredt
D S
DS
Dawson
T M
TM
Ronnett
G V
GV
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D015870:Gene Expression; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D051842:Olfactory Marker Protein; D009831:Olfactory Mucosa / Q000196:embryology*; D018034:Olfactory Receptor Neurons / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018035:Receptors, Odorant / Q000502:physiology*; D015398:Signal Transduction; D009435:Synaptic Transmission
D009419:Nerve Tissue Proteins; D051842:Olfactory Marker Protein; C497599:Omp protein, rat; D012333:RNA, Messenger; D018035:Receptors, Odorant; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases