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May 30, 2022
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Olfactory neurons adapt to the environment

Olfactory neurons adapt to the environment

Olfactory receptors, located on the surface of sensory neurons in the nasal cavity, recognize odor molecules and relay this information to the brain. How do these neurons manage to recognize a wide variety of signals and adapt to different levels of stimulation?

A collaborative team from the Faculty of Science and the Faculty of Medicine of the University of Geneva (UNIGE) investigated the gene expression profile of these neurons in the presence or absence of odor stimulation. The scientists found an unexpected variability in these profiles depending on the severity of the olfactory receptor and previous exposure to odors. These results, which will be published in the journal Nature Communications, provide evidence of a wide range of olfactory neuron identities and environmental adaptations.

In mammals, the perception of odors is provided by millions of olfactory neurons located in the mucous membrane of the nasal cavity. These neurons have receptors on their surface that can specifically bind to the odor molecule. Each olfactory neuron expresses only one gene encoding an olfactory receptor selected from a repertoire of about 450 in humans and 1,200 in mice.

When the volatile molecule is recognized by the receptor, it is activated and generates a signal that is transmitted to the olfactory bulb in the brain, a signal that is then converted into an odor. The olfactory system responds to a highly variable environment and must be able to adapt quickly. For example, with continuous stimulation by certain odor molecules, the intensity of perception gradually decreases, and sometimes completely disappears.

The group of Prof. Ivan Rodriguez, Department of Genetics and Evolution, Faculty of Science, in collaboration with Prof. Alan Carleton, Department of Basic Neuroscience, School of Medicine, is interested in the adaptive mechanisms of neurons, in particular olfactory neurons in mice. In a previous study, scientists found that after less than an hour of stimulation of a receptor by an odorant molecule, the expression of the gene encoding this receptor in a neuron decreases, indicating a very rapid adaptation mechanism.

Biologists have taken this approach further and explored the possibility that this adaptation to the olfactory experience affects not only the gene encoding the receptor, but also other genes. To do this, thousands of olfactory neurons were profiled for the genes expressed before and after olfactory stimulation by sequencing their messenger RNAs (molecules that subsequently allow proteins to be produced).

“To our surprise, we found that at rest, i.e. in an unstimulated environment, the messenger RNA profiles of mouse olfactory sensory neuron populations are already very different from each other and specific for the olfactory receptor they express,” reports Luis Flores Jorge. , doctoral student of the Department of Genetics and Evolution and co-author of the study. Neurons expressing the same receptor not only share a common receptor, but also differ in the expression of hundreds of other genes. Genes whose expression level appears to be directed by a prominent olfactory receptor, which thus plays a dual role.

The biologists then analyzed gene expression in these neurons after being stimulated by odorant molecules. They noticed that these molecules cause massive changes in gene expression in activated neurons. “While it was believed that the binding of an odorant molecule only leads to the activation of the corresponding receptor, we found that olfactory neurons radically change their identity, modulating the expression of hundreds of genes after activation. And this new identity again depends on the expressed receptor. Here we have an unexpected, large-scale, rapid and reversible mechanism of adaptation,” explains Ivan Rodriguez, co-author of the study.

This work shows that olfactory neurons should not be viewed as sensors simply moving from a resting state to a stimulated state, but that their identity is in constant evolution, not only depending on the expressed receptor, but also on past experience. This discovery adds another layer to the complexity and flexibility of the olfactory system. Understanding how this identity is defined will be the next challenge for the Geneva team.

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