The last week of June ushers in the 2024 International Symposium on Olfaction and Taste (ISOT), heralded as the world’s largest conference in the field. As scientists, industry experts, and trainees all come together to discuss emerging trends, the following review scent-ers on the latest olfaction discoveries.

Featured image (adapted from Parnas et al. (2024), ©2024 Elsevier B.V. All rights reserved.) demonstrating the differentiation of synthetic human lung cancer breath VS. synthetic healthy breath by the honeybee antennal lobe neuronal (ALN) responses. A) Odour delivery and neural recording setup. B) Table of six volatile organic compounds. C) Neural voltage responses of a representative ALN recording. D) Root mean squared filtering. E) Pairwise distance plots.

Precision detection of select human lung cancer biomarkers and cell lines using honeybee olfactory neural circuitry as a novel gas sensor

Honeybees are known to possess a particularly sensitive olfactory system, enabling the reliable detection of chemicals, scents, and odour mixtures. Leveraging this far-reaching capability, Parnas et al. (2024) tested whether the honeybee neural circuitry could detect lung cancer biomarkers.

To achieve this, ‘synthetic lung cancer’ and ‘synthetic healthy’ human breath were created by mixing different concentrations of human lung cancer volatile biomarkers. These mixtures were precisely delivered to the honeybee antenna using the 220A olfactometer. Further validation was performed by delivering the odour of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell cultures. Remarkably, in-vivo neural recordings from the honeybee brain revealed distinct spiking response dynamics in antennal lobe neurons in response to the biomarker mixtures and cell culture samples. These findings highlight how the honeybee olfactory system could be employed as a promising, sensitive biological gas sensor to detect human lung cancer, and could potentially improve diagnoses within the field.

Endogenous cannabinoids in the piriform cortex tune olfactory perception

The endogenous cannabinoid system (ECS) is a neuromodulator system comprised of cannabinoid receptors, endogenous cannabinoids (commonly called endocannabinoids), and endocannabinoid enzymes. Specifically, endocannabinoids are lipid-based neurotransmitters that bind to cannabinoid receptors in the body and are involved in an array of physiological processes, such as mood, memory, pain sensation, and appetite. While extensive research has been conducted on the ECS, how it influences sensory processing in the olfactory piriform cortex (aPC) region of the brain remains unclear.

Therefore, Terral et al. (2024) sought to explore how cannabinoid-type-1-receptors (CB1Rs) in the aPC influence olfactory perception. The researchers administered the CB1R antagonist, Rimonabant, to freely moving mice implanted with aPC probes. Fiber photometry experiments were subsequently conducted in the presence of odourants, which were delivered by the 220A olfactometer and validated with the 200B miniPID. Upon analysis, Rimonabant was found to have increased gamma oscillations and decreased synchronized population events in the aPC, leading to a reduced sensitivity to odours. These findings indicate that endocannabinoids in the aPC region effectively tune the neural processing and perception of odours.

A mechanosensory feedback that uncouples external and self-generated sensory responses in the olfactory cortex

An intriguing area of olfactory research is the relationship between odour inhalation speed, concentration, and perception. While faster sniffs are known to increase the magnitude of odour responses of mitral/tufted (MT) neurons, humans and rodents alike can effectively distinguish the concentration of odours regardless of inhalation speed. In an effort to understand this, Dehaqani et al. (2024) studied how sniffing influences odour perception in the piriform cortex (PCx) of awake, head-fixed mice.

Using Neuropixels 1.0 probes, inhalation responses to different odour concentrations were recorded. The odourants were delivered using a custom-made Arduino-controlled olfactometer, and validated with the 200B miniPID. Upon monitoring, they found that PCx activity effectively encoded the phase and speed of each inhalation, and that PCx neurons encoded the inhalation airflow rate in the nasal cavity. Importantly, the mechanosensory responses during inhalation were uncorrelated with olfactory responses within and between neurons. Therefore, the cortex was found to adapt to different inhalation speeds and concentration changes by adjusting cortical activity patterns. These results ultimately demonstrate how the PCx ensures reliable odour perception, even upon variations in inhalation speed.

Conclusions

The olfaction research realm encompasses a multitude of techniques, models, and applications. By providing a proof-of-concept for a novel biological sensor and delineating odour perception in the piriform cortex, these studies by Parnas et al. (2024), Terral et al. (2024), and Dehaqani et al. (2024) underscore the widespread contributions of olfaction research. Together, these novel insights have profound implications on the development of innovative technologies and our understanding of cognitive function.