Abstract

Binding of odorants to olfactory receptors (ORs) elicits downstream chemical and neural signals, which are further processed to odor perception in the brain. Recently, Mainland and colleagues have measured more than 500 pairs of odorant-OR interaction by a high-throughput screening assay method, opening a new avenue to understanding the principles of human odor coding. Here, using a recently developed minimal model for OR activation kinetics, we characterize the statistics of OR activation by odorants in terms of three empirical parameters: the half-maximum effective concentration EC50, the efficacy, and the basal activity. While the data size of odorants is still limited, the statistics offer meaningful information on the breadth and optimality of the tuning of human ORs to odorants, and allow us to relate the three parameters with the microscopic rate constants and binding affinities that define the OR activation kinetics. Despite the stochastic nature of the response expected at individual OR-odorant level, we assess that the confluence of signals in a neuron released from the multitude of ORs is effectively free of noise and deterministic with respect to changes in odorant concentration. Thus, setting a threshold to the fraction of activated OR copy number for neural spiking binarizes the electrophysiological signal of olfactory sensory neuron, thereby making an information theoretic approach a viable tool in studying the principles of odor perception.

Highlights

  • Olfaction, ubiquitous among all animals, is a key sensory process that is used to detect a vast number of chemicals in the external world [1, 2]

  • Since qualitatively similar trend is observed in the histogram for the entire ensemble of odorant-olfactory receptors (ORs) pairs as shown in Fig 3a, we assume that it effectively represents a general sensitivity profile of any odorant against the pool of human ORs; in other words, we hypothesize that the variable log10 CO displays the identical distribution ψens(log10 CO) as ψens(EC50) though ψens was constructed as a distribution of EC50 values

  • The present work makes an important step forward in this direction by analyzing the sub-cellular process of olfactory sensing within the olfactory receptor neuron (ORN) cell, at a scale larger than the individual molecular interactions but smaller than the multi-cell signal

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Summary

Introduction

Ubiquitous among all animals, is a key sensory process that is used to detect a vast number of chemicals in the external world [1, 2]. From the perspective of molecular recognition, the physicochemical principle germane to the early layer of olfactory process is not significantly different from that of unicellular organisms’ chemotactic response [3,4,5]. Olfactory signals are initiated upon the recognition of odorants by the receptors that are expressed in the nasal epithelium [6]. Physiological and biochemical studies of olfaction to date offer strong evidence that the majority of mammalian OR signalings are associated with G-protein dependent pathway [7]. A set of ORs adopt their structures into active forms and catalyze G-proteins to initiate downstream signal cascades

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