Dynamic switch between ON and OFF responses in an olfactory receptor neuron

It has been shown that sensory neurons are either activated or inhibited by stimuli. Here we demonstrate existence of a third response modality in the Drosophila olfactory receptor neuron (ORN) ab2A, whose polarity is inverted from excitatory to inhibitory when stimulated with a single odorant of a certain type. ab2A increases its spike rate in response to an initial increase in odor intensity, exhibiting an “on” response. However, further increases/decreases in stimulus intensity elicit a decrease/increase in the spike rate, reminiscent of “off” responses.  This on/off polarity inversion is dose-dependent and modulates olfactory behavior. It is broadly observed across several odorants and with other drosophilids. Furthermore, ab2A can compute whether an odor is a mixture of inverting and non-inverting odorants, as well as whether an inverting odor is received as a background or foreground cue. Polarity inversion does not require electrical coupling with neighboring neurons, does not rely on extracellular molecular mechanisms, and is not a result of membrane depolarization. Inversion is observed at the level of signal transduction, upstream of action potential generation. Moreover, it is qualitatively recapitulated by a biophysical model with two binding sites, suggesting it might take place at the level of the receptor. Together, these results establish polarity inversion as an important property of ORNs, and provide a quantitative framework for future studies of this new dimension in odor coding and neural computation.