The role of cGMP in olfactory signaling is not fully understood, but i
t is believed to play a modulatory role in intracellular signaling in
vertebrate olfactory receptor neurons (ORNs). Here, we present evidenc
e that cGMP in ORNs may play an important role in recognition of biolo
gically relevant odors and olfactory learning. Specifically, we invest
igated the cellular mechanisms underlying olfactory imprinting in salm
on. Salmon learn odors associated with their natal site as juveniles a
nd later use these odors to guide their homing migration. This imprint
ing is believed to involve sensitization of the peripheral olfactory s
ystem to specific homestream odorants. We imprinted juvenile salmon to
the odorant beta-phenylethyl alcohol (PEA) and examined the sensitivi
ty of olfactory adenylyl and guanylyl cyclases to PEA during developme
nt. Stimulation of guanylyl cyclase activity by PEA was significantly
greater in olfactory cilia isolated from PEA-imprinted salmon compared
with PEA-naive fish only at the time of the homing migration, 2 years
after PEA exposure. These results suggest that sensitization of olfac
tory guanylyl cyclase may play an important role in olfactory imprinti
ng by salmon.