There are at least 400 odorant receptors expressed in the human nose. This allows one to differentiate between a large number of scents. The number of odor receptors is closer to 1000 in mice. Each olfactory neuron exhibits only a single type of receptor. Furthermore, all neurons with the same receptors are connected to the glomerulus in the brain forming an olfactory map. This map is significant because it serves as a codebook for odorants. It permits the brain to decide between food odors and the scent of a predator, among others.
Olfactory neurons have the exclusive capacity to regenerate throughout life. More remarkably, the regenerated neurons must send off their axons on a path through the nasal epithelium to the brain. There they make the proper connections and if regenerating neurons are mis-wired to different glomeruli, odor perception would change.
The journal Science published a study, conducted at the Stowers Institute of Medical Research. It identifies a developmental window during which olfactory neurons of newborn mice can form a proper olfactory map. The research team shows that if wrong neuronal connections are retained after this period, renewing cells will also be mis-wired.
Moreover, the results of the study hint at the connection of olfactory neurons to their respective targets. They suggest additional targeting skills that stem cell-generated neurons need to attain in order to repair the brain or spinal cord.
Previously, researchers believed that as the olfactory neurons exhibit lifelong regeneration, they are likely to retain the ability to re-establish correct connections. However, this isn’t the case.
What did the research team do?
For the study, the research team used a number of transgenic mouse lines. They worked to reveal that the first week after birth is the crucial time for restoring normal projections. If mis-targeting isn’t rectified within this period, many cells get locked onto the wrong tracks after regeneration.
Researchers created a genetically engineered mouse in which they could silence the firing of olfactory neurons temporarily which caused them to connect to the wrong glomeruli. Furthermore, if these inactivated sensory neurons were reactivated within a week of a mouse’s birth, incorrect olfactory neuron connections were restored. However, beyond that critical period, the neurons appeared to lose the capacity to make the right connections.
Research specialists comment that after the first week, the newly generated neurons follow pre-existing tracks to their target. This point was proved by provoking a temporary identity crisis in olfactory neurons. Scientists broadly mis-expressed an odorant receptor called M71 in cells where it would not normally be displayed. The research team was intrigued to find that only the neurons that normally express the M71 receptor targeted the wrong glomeruli and not the neurons that express different odorant receptors.
The research team interpreted that late-born olfactory neurons, expressing a particular receptor, identify and chase a track laid down earlier by neurons expressing the very same receptor. The condition holds even if the latter expressed that receptor due to experimental manipulation. These olfactory neurons have identity tags and they like to follow others displaying the same tag.
As yet, investigators have not identified the molecular basis for the targeting switch. They don’t know what keeps these late-stage cells from re-establishing the right connections. Thus, the researchers are intending to further their studies so that they can investigate how a regenerated neuron finds their right connecting target.