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 input-output (I/O) relationships. Up to this point, our accounts of the systems go along similar lines. The next processing steps differ considerably: whereas 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 has there 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.

The perception of odors is influenced by a variety of neuromodulators, and there is growing evidence that modulation already takes place in the olfactory epithelium. Here we report on cannabinergic actions in the olfactory epithelium of Xenopus laevis tadpoles. First we show that CB1 receptor-specific antagonists AM251, AM281, and LY320135 modulate odor-evoked calcium changes in olfactory receptor neurons. Second, we localize CB1-like immunoreactivity on dendrites of olfactory receptor neurons. Finally, we describe the cannabinergic influence on odor-induced spike-associated currents in individual olfactory receptor neurons. Here we demonstrate that the cannabinergic system has a profound impact on peripheral odor processing and discuss its possible function.

Aggregation and spreading of α-Synuclein (αSyn) are hallmarks of several neurodegenerative diseases, thus monitoring human αSyn (hαSyn) in animal models or cell cultures is vital for the field. However, the detection of native hαSyn in such systems is challenging. We show that the nanobody NbSyn87, previously-described to bind hαSyn, also shows cross-reactivity for the proteasomal subunit Rpn10. As such, when the NbSyn87 is expressed in the absence of hαSyn, it is continuously degraded by the proteasome, while it is stabilized when it binds to hαSyn. Here, we exploit this feature to design a new Fluorescent Reporter for hαSyn (FluoReSyn) by fusing NbSyn87 to fluorescent proteins, which results in fluorescence signal fluctuations depending on the presence and amounts of intracellular hαSyn. We characterize this biosensor in cells and tissues to finally reveal the presence of transmittable αSyn in human cerebrospinal fluid, demonstrating the potential of FluoReSyn for clinical research and diagnostics.

Cannabinoids modulate the activity of many neuronal cells, among them sensory neurons in the olfactory epithelium. Here we show that the endocannabinoid 2-arachidonoyl-glycerol (2-AG) is synthesized in both olfactory receptor neurons and glia-like sustentacular cells in larval Xenopus laevis. Its production in the latter depends on the hunger state of the animal. The essential effect of 2-AG in olfactory receptor neurons is the control of odorant detection thresholds via cannabinoid CB₁ receptor activation. Hunger renders olfactory neurons more sensitive. Endocannabinoid modulation in the nose may therefore substantially influence food-seeking behavior.

Mammalian olfactory receptor families are segregated into different olfactory organs, with type 2 vomeronasal receptor ( v2r ) genes expressed in a basal layer of the vomeronasal epithelium. In contrast, teleost fish v2r genes are intermingled with all other olfactory receptor genes in a single sensory surface. We report here that, strikingly different from both lineages, the v2r gene family of the amphibian Xenopus laevis is expressed in the main olfactory as well as the vomeronasal epithelium. Interestingly, late diverging v2r genes are expressed exclusively in the vomeronasal epithelium, whereas “ancestral” v2r genes, including the single member of v2r family C, are restricted to the main olfactory epithelium. Moreover, within the main olfactory epithelium, v2r genes are expressed in a basal zone, partially overlapping, but clearly distinct from an apical zone of olfactory marker protein and odorant receptor-expressing cells. These zones are also apparent in the spatial distribution of odor responses, enabling a tentative assignment of odor responses to olfactory receptor gene families. Responses to alcohols, aldehydes, and ketones show an apical localization, consistent with being mediated by odorant receptors, whereas amino acid responses overlap extensively with the basal v2r -expressing zone. The unique bimodal v2r expression pattern in main and accessory olfactory system of amphibians presents an excellent opportunity to study the transition of v2r gene expression during evolution of higher vertebrates.

Olfactory receptor neurons (ORNs) are the only class of neurons that is directly exposed to the environment. Therefore, they need to deal with xenobiotic and potentially cytotoxic substances. Here we show for the first time that ORNs possess transporter systems that expel xenobiotics across the plasma membrane. Using calcein and calcium-indicator dyes as xenobiotics, we demonstrate that ORNs appear to express the multidrug resistance P-glycoprotein (MDR1) and multidrug resistance-associated proteins (MRP). This endows ORNs with the ability to transport a large number of substrates including calcium-indicator dyes and calcein across their plasma membranes. Conversely, blocking P-glycoprotein and MRP increases the net uptake of these dyes.