TY - JOUR T1 - Differential Electrophysiological Responses to Odorant Isotopologues In Drosophilid Antennae JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0152-15.2016 SP - ENEURO.0152-15.2016 AU - Efstathia Drimyli AU - Alexandros Gaitanidis AU - Klio Maniati AU - Luca Turin AU - Efthimios MC Skoulakis Y1 - 2016/05/31 UR - http://www.eneuro.org/content/early/2016/05/30/ENEURO.0152-15.2016.abstract N2 - Olfaction presents the ultimate challenge to molecular recognition as thousands of molecules have to be recognized by far fewer olfactory receptors. We have presented evidence that Drosophila readily distinguish odorants based on their molecular vibrations using a battery of behavioral assays suggesting engagement of a molecular vibration-sensing component. Here we interrogate electrophysiologically the antennae of four Drosophilids and demonstrate conserved differential response amplitudes to aldehydes, alcohols, ketones, nitriles and their deuterated isotopologues. Certain deuterated odorants evoked larger electroantennogram (EAG) amplitudes, while the response to the normal odorant was elevated in others. Significantly, benzonitrile isotopologues were not distinguishable as predicted. This suggests that isotopologue-specific EAG amplitudes result from differential activation of specific olfactory receptors. In support of this, odorants with as few as two deuteria evoke distinct EAG amplitudes from their normal isotopologues and this is independent of the size of the deuterated molecule. Importantly, we find no evidence that these isotopologue-specific amplitudes depend on perireceptor mechanisms or other pertinent physical property of the deuterated odorants. Rather, our results strongly suggest that Drosophilid olfactory receptors are activated by molecular vibrations differentiating similarly sized and shaped odorants in vivo, yielding sufficient differential information to drive behavioral choices.Significance Statement: Insects can behaviorally discriminate odorants from their deuterated isotopologues. It remains unclear whether discrimination occurs because olfactory receptors detect their distinct molecular vibrations, or because isotopologues differ sufficiently in other properties to be perceived differentially. We report electrophysiological recordings, taken from the antennae of several Drosophilid species exposed to a range of odorant isotopologues. We find that in almost all cases of odorant and species tested, electroantennogram amplitude, but not kinetics, differs in response to hydrogen-only and deuterated odorants. Inhibition of enzymes that prevalently catabolize odorants has no effect on the isotopologue-specific response. Hence, we conclude that in vivo, isotopologue differentiation is not a perireceptor event, but likely occurs at the receptor itself. ER -