Research conducted at the Stowers Institute for Medical Research reports the identification of “navigator neurons” that are critically responsible for the sense of smell. This recent research is based on a breakthrough report by the Stowers laboratory in 2014. It demonstrated a critical period in olfactory wiring using mice as a model system.
The olfactory system comprises of a complex web of neural connections for detecting odors. The axons of the olfactory sensory neurons, in the nose, pass information to the olfactory bulb in the brain. Neurons of the similar receptors project their axons and connect to the same spot in the brain, called a glomerulus. This converging olfactory map acts as a kind of codebook for the fragrances we come across. Malfunctioning in the map’s wiring affects how we perceive the scents.
It was believed previously that olfactory neurons regenerate and replace themselves throughout the life of an animal. Moreover, it was thought that they possess the ability to re-establish correct connections. However, this study reveals that this isn’t the case.
What does the study say?
The researchers used a number of transgenic mouse lines for the study. They demonstrated that the first week after birth is critical to fix problems. If mis-targeting continues during this period, the cells still regenerate, but many of them get locked onto the wrong tracks.
The results of the study indicated that the map of neural connectivity is set early in life. For this purpose, nature has created a group of neurons that only exists during a critical period. The adult stage neurons do not possess this capacity. The researchers specified this surprising discovery of olfactory sensory neurons, playing an eminent role in establishing the olfactory map and correcting the faulty connections. The researchers termed them as navigator neurons.
Navigator neurons are structurally and functionally the same as neurons born later. Thus, it took various creative approaches for the researchers to finally pinpoint them.
The researchers carried out Chronogenetic tracking to trace a neuron’s lifespan using genetic labeling. They constructed an adenovirus carrying genes into the neurons with clearly labeled individual axons. Furthermore, the researchers combined virus labeling and CLARITY for obtaining entire trajectories of axon projection into the olfactory bulb. It is a technique that makes samples of mouse brain tissue transparent for distinguishing the axon projected in.
Moreover, the researchers opted for single-cell transcriptome analysis for,
- Characterizing the molecular identity of the cells
- Detecting changes in gene expression during development
All of these methods demonstrated distinct characteristics of the navigator neurons as compared to the olfactory sensory neurons.
What do the findings suggest?
The researchers suggest that extending the lifespan of navigator neurons prolongs their period of exuberant growth and stops the convergence of the axons. Navigator neurons also have very different trajectories while projecting during early development. They roam around instead of going straight to the glomeruli. This behavior rectifies improper connections and initiates new connections by sampling a much larger area.
During trauma-related anosmia, the sense of smell is lost. This is because of the severing of connection from sensory neurons to the olfactory bulb. When the axons get cut they might regenerate. However, if they cannot reform the firm connections properly, one would still lose the sense of smell.
The role of the navigator neurons in establishing olfactory map wiring promises regeneration and repairing of the olfactory neurons. They may also help neurons in other types of neural systems, such as those involved in spinal cord injury.