Phosphoinositide 3-Kinase Dependent Inhibition as a Broad Basis for Opponent Coding in Mammalian Olfactory Receptor Neurons

Kirill Ukhanov,Elizabeth A Corey,Barry W Ache,Johannes Reisert

doi:10.1371/journal.pone.0061553

Kirill Ukhanov, Elizabeth A Corey + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0061553

Copy DOI

Abstract

Phosphoinositide 3-kinase (PI3K) signaling has been implicated in mediating inhibitory odorant input to mammalian olfactory receptor neurons (ORNs). To better understand the breadth of such inhibition in odor coding, we screened a panel of odorants representing different chemical classes, as well as odorants known to occur in a natural odor object (tomato), for their ability to rapidly activate PI3K-dependent inhibitory signaling. Odorants were screened on dissociated native rat ORNs before and after pre-incubation with the PI3K-isoform specific blockers AS252424 and TGX221. Many different odorants increased their excitatory strength for particular ORNs following PI3K blockade in a manner consistent with activating PI3K-dependent inhibitory signaling in those cells. The PI3K-dependent inhibitory odorants overlapped with conventional excitatory odorants, but did not share the same bias, indicating partial partitioning of the odor space. Finding that PI3K-dependent inhibition can be activated by a wide range of otherwise conventional excitatory odorants strongly implies PI3K-dependent inhibition provides a broad basis for opponent coding in mammalian ORNs.

Highlights

Odor recognition is not just a simple summation of responses to the components of an odorant mixture
To address the question of whether there are dedicated PI3Kdependent inhibitory odorants, we began by assembling a panel of 42 conventional odorants, all of which are known to elicit olfactory responses in rodents
We demonstrated that activation of rat olfactory receptor neurons (ORNs) could be inhibited in a phosphoinositide 3-kinase (PI3K)-dependent manner by studying a few inhibitory odorant pairs in detail [14,15]

Summary

Introduction

Odor recognition is not just a simple summation of responses to the components of an odorant mixture. Odor recognition is known to be a distributed phenomenon, one that begins at the level of the olfactory receptor neuron (ORN), where different odorants generate complex patterns of activation ranging from strong activation to complete inhibition. Antagonists structurally related to known agonists, e.g., methyl isoeugenol versus eugenol, can directly interfere with ORN activation in a manner indicative of, or at least strongly suggestive of, competitive inhibition at the binding pocket of the olfactory receptor (OR) [9,10,11,12,13]. Chemically dissimilar odorants that vary in agonistic strength, e.g., citral versus octanol, can inhibit mammalian ORNs in a phosphoinositide 3-kinase (PI3K)-dependent manner [14,15], suggesting a different mechanism of antagonism or opposition in which odorants rapidly activate an opponent signaling pathway

Methods

Results

Conclusion