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Neural wiring of smell settles shortly after birth, study finds

University neuroscientists find that olfactory connections are fixed soon after birth in mice

A mouse’s sense of smell remains fairly constant after its first week of life, according to a study published in the journal Science last Friday.

While a mouse can regenerate olfactory neuron connections — the wiring of smell — throughout its lifetime, researchers found the wiring pattern is essentially determined during early development.

To study the development of this portion of the nervous system, the researchers inserted a gene that is not normally expressed — MOR28, which codes for a specific odorant receptor in the nose —  into groups of mice. By marking this inserted gene, called a transgene, with a red indicator and the normal genes with a green indicator and activating it at different early stages of development, the researchers determined the location and timing of the growth of this odorant receptor.

Adult mice exhibit an olfactory wiring pattern that is essentially fixed, said Gilad Barnea, assistant professor of neuroscience and corresponding author of the study. When chemicals in the air interact with receptors in the nose, the signal is transmitted to glomeruli in the olfactory bulb, Gilad said. The position of individual glomeruli is unique to each odorant receptor. Projection neurons from the olfactory bulb then connect to higher brain areas, resulting in the sensation of smell, he added.

The researchers found that if the transgene was activated at a specific time during development, it caused neurons to grow differently than in mice without the transgene. Normally, each odorant receptor connects with a structure called a glomerulus at a specific location in the olfactory bulb — a part of the brain near the nose. But when the transgene was activated in early development, neural connections in the glomerulus were rerouted. The authors wrote in the study that this rerouting was due to the presence of different receptors in the nose.

There appears to be a “critical period” during which the olfactory wiring is still plastic, said Lulu Tsai PhD’13, lead author of the study and a postdoctoral fellow at Drexel University. Tsai completed this research for her graduate thesis.

Tsai and Barnea also examined whether the adult mouse nervous system regenerates new neurons later in life based on patterns of growth during development. They found that when regrowth of neurons occurs, the wiring is still dictated by both the transgene and the endogenous genes. This suggests that the adult mouse system holds memories of its wiring pattern during development.

Studying how axons — the wires of the nervous system — grow to reach different cells is one of the most important parts of understanding neural development, Tsai said. A cell’s main function is to communicate with other cells in the body, so if a neuron cannot transmit information to the correct population of neurons, it is effectively useless, she added.

The present study’s findings have large implications for our understanding of how events early in gestation could affect the rest of an organism’s life, such as when a pregnant woman smokes or drinks, Barnea said. “What happens at birth stays for life.”

While this study highlights the importance of the critical period in olfactory development, there is still much work to be done in exploring how the theoretical implications of the study relate more broadly to neural development, said Leonardo Belluscio, a senior investigator at the Developmental Neural Plasticity Section of the National Institutes of Health. Tsai and Barnea focused on one particular set of neurons — those coded for by the MOR28 gene — which does not necessarily mean the findings can be extrapolated to other parts of the nervous system, he added.

The study’s findings can be viewed in either a positive or a negative light, Tsai said. On the negative end, a person born with a nervous system condition may have some sort of neural memory that could prevent curative procedures such as stem cell therapy. But on the positive side, a person who undergoes a traumatic injury later in life may be able to rely on the system’s memory to reestablish the original neural connections, she added.


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