Encoding of odors by mammalian olfactory receptors

Olfactory receptors (ORs) constitute the largest multi-gene family in the mammalian genome, with hundreds to thousands of loci in humans and mice respectively. The rapid expansion of this massive family of genes has been generated by numerous duplication and diversification events throughout evolutionary history. This size, similarity, and diversity has made it challenging to define the principles by which ORs encode olfactory stimuli. Here, we performed a broad surveying of OR responses, using an in vivo strategy, against a diverse panel of odorants. We then used the resulting interaction profiles to uncover relationships between OR responses, odorants, odor molecular properties, and OR sequences. Our data and analyses revealed that ORs generally exhibited sparse tuning towards odorants and their molecular properties. Odor molecular property similarity between pairs of odorants was informative of odor response similarity. Finally, ORs sharing response to an odorant possessed amino acids at poorly conserved sites that exhibited both, predictive power towards odorant selectivity and convergent evolution. The localization of these residues occurred primarily at the interface of the upper halves of the transmembrane domains, implying that canonical positions govern odor selectivity across ORs. Altogether, our results provide a basis for translating odorants into receptor neuron responses for the unraveling of mammalian odor coding.

Higher-order olfactory neurons in the lateral horn supports odor valence and odor identity coding in Drosophila

Understanding neuronal representations of odor-evoked activities and their progressive transformation from the sensory level to higher brain centers features one of the major aims in olfactory neuroscience. Here, we investigated how odor information is transformed and represented in higher-order neurons of the lateral horn, one of the higher olfactory centers implicated in determining innate behavior, using Drosophila melanogaster. We focused on a subset of third-order glutamatergic lateral horn neurons (LHNs) and characterized their odor coding properties in relation to their presynaptic partner neurons, the projection neurons (PNs) by two-photon functional imaging. We found that odors evoke reproducible, stereotypic and odor-specific response patterns in LHNs. Notably, odor-evoked responses in these neurons are valence-specific in a way that their response amplitude is positively correlated with innate odor preferences. We postulate that this valence-specific activity is the result of integrating inputs from multiple olfactory channels through second-order neurons. GRASP and micro-lesioning experiments provide evidence that glutamatergic LHNs obtain their major excitatory input from uniglomerular PNs, while they receive an odor-specific inhibition through inhibitory multiglomerular PNs. In summary, our study indicates that odor representations in glutamatergic LHNs encode hedonic valence and odor identity and primarily retain the odor coding properties of second-order neurons.

Chronic exposure to odors at naturally occurring concentrations triggers limited plasticity in early stages of Drosophila olfactory processing

ABSTRACTIn insects and mammals, chronic exposure to odors at high concentrations in early life alters olfactory function, but the role of odor experience-dependent plasticity in more naturalistic contexts is less clear. We investigated olfactory plasticity in the Drosophila antennal lobe by exposing flies to odors at concentrations that are typically encountered in natural odor sources. These stimuli also strongly and selectively activated only a single class of olfactory receptor neuron (ORN) input, facilitating the investigation of input-specific plasticity. Overall, chronic exposure to three such odors elicited limited plasticity in the odor responses of second-order projection neurons (PNs). Exposure to some odors elicited mild increases in PN responses to weak stimuli, extending the lower bound of the dynamic range of PN signaling. When present, plasticity was observed broadly in multiple PN types and thus was not selective for PNs receiving direct input from the chronically active ORNs. Chronic E2-hexenal exposure did not affect PN intrinsic properties, local inhibitory innervation, ORN responses, or ORN-PN synaptic strength, but modestly increased broad lateral excitation evoked by some odors. These results show that PN odor coding is only mildly affected by strong persistent activation of a single olfactory input and highlight the stability of early stages of insect olfactory processing to significant perturbations in the sensory environment.

Olfactory Optogenetics: Light Illuminates the Chemical Sensing Mechanisms of Biological Olfactory Systems

The mammalian olfactory system has an amazing ability to distinguish thousands of odorant molecules at the trace level. Scientists have made great achievements on revealing the olfactory sensing mechanisms in decades; even though many issues need addressing. Optogenetics provides a novel technical approach to solve this dilemma by utilizing light to illuminate specific part of the olfactory system; which can be used in all corners of the olfactory system for revealing the olfactory mechanism. This article reviews the most recent advances in olfactory optogenetics devoted to elucidate the mechanisms of chemical sensing. It thus attempts to introduce olfactory optogenetics according to the structure of the olfactory system. It mainly includes the following aspects: the sensory input from the olfactory epithelium to the olfactory bulb; the influences of the olfactory bulb (OB) neuron activity patterns on olfactory perception; the regulation between the olfactory cortex and the olfactory bulb; and the neuromodulation participating in odor coding by dominating the olfactory bulb. Finally; current challenges and future development trends of olfactory optogenetics are proposed and discussed.

Principles of odor coding in vertebrates and artificial chemosensory systems

The biological olfactory system is the sensory system responsible for the detection of the chemical composition of the environment. Several attempts to mimic biological olfactory systems have led to various artificial olfactory systems using different technical approaches. Here we provide a parallel description of biological olfactory systems and their technical counterparts. We start with a presentation of the input to the systems, the stimuli, and treat the interface between the external world and the environment where receptor neurons or artificial chemosensors reside. We then delineate the functions of receptor neurons and chemosensors as well as their overall I-O relationships. Up to this point, our account of the systems goes along similar lines. The next processing steps differ considerably: while in biology the processing step following the receptor neurons is the "integration" and "processing" of receptor neuron outputs in the olfactory bulb, this step has various realizations in electronic noses. For a long period of time, the signal processing stages beyond the olfactory bulb, i.e., the higher olfactory centers were little studied. Only recently there has been a marked growth of studies tackling the information processing in these centers. In electronic noses, a third stage of processing has virtually never been considered. In this review, we provide an up-to-date overview of the current knowledge of both fields and, for the first time, attempt to tie them together. We hope it will be a breeding ground for better information, communication, and data exchange between very related but so far little connected fields.

Genome-wide survey of odorant-binding proteins in the dwarf honey bee Apis florea

Odorant binding proteins (OBPs) in insects bind to volatile chemical cue and help in their binding to odorant receptors. The odor coding hypothesis states that OBPs may bind with specificity to certain volatiles and aid the insect in various behaviours. Honeybees are eusocial insects with complex behaviour that requires olfactory inputs. Here, we have identified and annotated odorant binding proteins from the genome of the dwarf honey bee, Apis florea using an exhaustive homology-based bioinformatic pipeline and analyzed the evolutionary relationships between the OBP subfamilies. Our study suggests that Minus-C subfamily may have diverged from the Classic subfamily of odorant binding proteins in insects.

Odor coding in the mammalian olfactory epithelium

Noses are extremely sophisticated chemical detectors allowing animals to use scents to interpret and navigate their environments. Odor detection starts with the activation of odorant receptors (ORs), expressed in mature olfactory sensory neurons (OSNs) populating the olfactory mucosa. Different odorants, or different concentrations of the same odorant, activate unique ensembles of ORs. This mechanism of combinatorial receptor coding provided a possible explanation as to why different odorants are perceived as having distinct odors. Aided by new technologies, several recent studies have found that antagonist interactions also play an important role in the formation of the combinatorial receptor code. These findings mark the start of a new era in the study of odorant-receptor interactions and add a new level of complexity to odor coding in mammals.

Odor Coding in the Mammalian Olfactory Epithelium

Noses are extremely sophisticated chemical detectors allowing animals to use scents to interpret and navigate their environments. Odor detection starts with the activation of odorant receptors (ORs), expressed in mature olfactory sensory neurons (OSNs) populating the olfactory mucosa. Different odorants, or different concentrations of the same odorant, activate unique ensembles of ORs. This mechanism of combinatorial receptor coding provided a possible explanation as to why different odorants are perceived as having distinct odors. Aided by new technologies, several recent studies have found that antagonist interactions also play an important role in the formation of the combinatorial receptor code. These findings mark the start of a new era in the study of odorant-receptor interactions and add a new level of complexity to odor coding in mammals.

Young adult-born neurons improve odor coding by mitral cells

New neurons are continuously generated in the adult brain through a process called adult neurogenesis. This form of plasticity has been correlated with numerous behavioral and cognitive phenomena, but it remains unclear if and how adult-born neurons (abNs) contribute to mature neural circuits. We established a highly specific and efficient experimental system to target abNs for causal manipulations. Using this system with chemogenetics and imaging, we found that abNs effectively sharpen mitral cells (MCs) tuning and improve their power to discriminate among odors. The effects on MCs responses peaked when abNs were young and decreased as they matured. To explain the mechanism of our observations, we simulated the olfactory bulb circuit by modelling the incorporation of abNs into the circuit. We show that higher excitability and broad input connectivity, two well-characterized features of young neurons, underlie their unique ability to boost circuit computation.