Researchers have found evidence that support cells that surround olfactory neurons make a more important contribution to perception than previously assumed.Credit: A Hernandez-Clavijo et al/ iScience 107186, JULY 2023

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Neuroscientists have for the first time measured the electrical activity of individual cells extracted from human olfactory tissues and exposed to different smells. The study was coordinated by the International School of Advanced Studies (SISSA) and could also help reveal how smell is affected by infection with SARS-CoV-2.

Smell is the least understood sense, but the fact that many patients partially or entirely lost it during the COVID-19 crisis has prompted neuroscientists to delve into it. “Neurons of the olfactory epithelium are the only neurons in direct contact with the external environment,” says Anna Menini, a professor at SISSA, in Trieste, Italy, who led the study, “but, until now we had no direct evidence of their functioning”.

The scientists performed biopsies on healthy subjects to take slices of the human olfactory epithelium, a tissue located in the back of the nasal cavity, which is where the perception of smells happens. The slices were then isolated, and recording devices were used to measure the cellular electrical response. The scientists used two different mixtures of compounds to stimulate the epithelium slices and found that the cells responded with specific electrical patterns to each.

In addition to showing that the method works, which paves the way for more studies, the researchers found evidence that support cells that surround olfactory neurons make a more important contribution to perception than previously assumed. These cells also represent the link between COVID-19 and the loss or decline of olfaction. “It is precisely the support cells, as indicated by previous research, that carry on their surface the ACE2 receptor,” says Menini. ACE2 is a protein, present in various tissues of the body, to which SARS-CoV-2 can bind, and when support cells are lost, olfactory neurons also die. But often all is not lost. “Neurons can regenerate,” says Menini, “thanks to specific stem cells, and in many cases the sense of smell is restored, although this can take time”.

Scientists have also hypothesized a mechanism by which, even in the presence of low viral loads, a knock-on effect leads to extensive involvement of supporting cells. “The hypothesis is that, as it was observed at the lung level in another study, large clusters are created from the fusion of several cells, called ‘syncitia’, in which even a single virus-infected supporting cell can cause several cells to fuse.” says Menini.

The next step will be to study the electrical response of olfactory tissues taken from people affected by COVID-19 and anosmia or other olfactory changes to better understand the mechanisms, and how recovery occurs.