Olfactory Sensory Neuron Diversity Measured By RNA Sequencing

What we perceive as smells are just chemicals in the air that are recognized by nerves in our nose. Each nerve has a receptor that can identify a limited number of chemicals, and the nerve then relays this information to the brain. Animals have hundreds to thousands of different types of these nerves meaning that they can detect a wide array of smells.

Smell receptors are proteins, and the genes that encode these proteins can be very different in two unrelated people. This could partly explain, for example, why some people find certain odors intense and unpleasant while others do not.

However, having different genes for smell receptors does not by itself completely explain why some people are more sensitive than others to particular smells. The amounts of each nerve type in the nose might also differ between people and have an effect, but to date it has not been possible to accurately count them all.

Smell Receptor Types

Ximena Ibarra-Soria, from the Wellcome Trust Sanger Institute in Cambridge, along with an international team of researchers, devised a new method to essentially count the number of each nerve type in the noses of mice from different breeds. The method makes use of a technique called RNA sequencing, which can reveal which genes are active at any one time, and thus show how many nerves are producing each type of smell receptor.

The researchers learned that different breeds of mice had remarkably different compositions of nerves in their noses. Further analysis revealed that this was due to changes to the DNA code near to the genes that encode the smell receptor.

OSN diversity is determined by the genetic background

OSN diversity is determined by the genetic background and not by the olfactory environment.
(A) Experimental strategy to differentiate genetic from environmental influences on OSN diversity. B6 (blue) and 129 (yellow) embryos, depicted as circles, were transferred into F1 recipient mothers (grey). After birth, the litters were cross-fostered to B6 and 129 mothers, respectively. Each B6 litter received one 129 pup (the alien) and vice versa. After 10 weeks, the WOM was collected for RNAseq from three aliens from each strain, and one cage-mate each.
(B) Heatmap of the expression of the OR genes (columns) in all 12 sequenced animals (rows). Samples cluster by the genetic background of the animals. The strain and environment of each mouse is indicated through shading (right).
(C) Differential expression analyses revealed mRNA from only two genes, Olfr875 and Olfr491, that are significantly altered based on the olfactory environment. Expression values are shown for each group. Blue and yellow boxes indicate B6 or 129 animals respectively, and the background indicates the olfactory environment.
DOI: http://dx.doi.org/10.7554/eLife.21476.009

Next, Ibarra-Soria sought to find out how the amount of each nerve type is controlled by giving mice water with different smells for weeks and looking how this affected their noses. These experiments revealed that a small number of the nerve types became more or less common after exposure to a smell.

The altered nerves were directly involved in recognizing the smells, proving that the very act of smelling can change the make-up of nerves in a mouse’s nose.

The results confirm that the diversity in the nose of each individual is not only dictated by the types of receptors found in there, but also by the number of each nerve type. The next challenge is to understand better how these differences change the way people perceive smells.

Ximena Ibarra-Soria Thiago S Nakahara Jingtao Lilue Yue Jiang Casey Trimmer Mateus AA Souza Paulo HM Netto Kentaro Ikegami Nicolle R Murphy Mairi Kusma Andrea Kirton Luis R Saraiva Thomas M Keane Hiroaki Matsunami Joel Mainland Fabio Papes Darren W Logan
Variation in olfactory neuron repertoires is genetically controlled and environmentally modulated
eLife 2017;6:e21476

Top Image: Ulrich von Andrian, M.D., Ph.D., Harvard Medical School/NIH. Sensory neurons (red) and dendritic cells (green) in mouse skin.