Quantum origins of molecular recognition and olfaction in Drosophila.

The standard model for molecular recognition of an odorant is that receptor sites discriminate by molecular geometry as evidenced that two chiral molecules may smell very differently. However, recent studies of isotopically labeled olfactants indicate that there may be a molecular vibration-sensing component to olfactory reception, specifically in the spectral region around 2300 cm(-1). Here, we present a donor-bridge-acceptor model for olfaction which attempts to explain this effect. Our model, based upon accurate quantum chemical calculations of the olfactant (bridge) in its neutral and ionized states, posits that internal modes of the olfactant are excited impulsively during hole transfer from a donor to acceptor site on the receptor, specifically those modes that are resonant with the tunneling gap. By projecting the impulsive force onto the internal modes, we can determine which modes are excited at a given value of the donor-acceptor tunneling gap. Only those modes resonant with the tunneling gap and are impulsively excited will give a significant contribution to the inelastic transfer rate. Using acetophenone as a test case, our model and experiments on D. melanogaster suggest that isotopomers of a given olfactant give rise to different odorant qualities. These results support the notion that inelastic scattering effects may play a role in discriminating between isotopomers but that this is not a general spectroscopic effect.

G(o) activation is required for both appetitive and aversive memory acquisition in Drosophila.

Heterotrimeric G(o) is an abundant brain protein required for negatively reinforced short-term associative olfactory memory in Drosophila. G(o) is the only known substrate of the S1 subunit of pertussis toxin (PTX) in fly, and acute expression of PTX within the mushroom body neurons (MB) induces a reversible deficit in associative olfactory memory. We demonstrate here that the induction of PTX within the α/ß and γ lobe MB neurons leads to impaired memory acquisition without affecting memory stability. The induction of PTX within these MB neurons also leads to a significant defect in an optimized positively reinforced short-term memory paradigm; however, this PTX-induced learning deficit is noticeably less severe than found with the negatively reinforced paradigm. Both negatively and positively reinforced memory phenotypes are rescued by the constitutive expression of G(o)α transgenes bearing the Cys(351)Ile mutation. Since this mutation renders the G(o) molecule insensitive to PTX, the results isolate the effect of PTX on both forms of olfactory associative learning to the inhibition of the G(o) activation.