That old familiar smell…

Abstract

It's a distinctly musty odor. I smell it, and it evokes powerful memories of childhood visits to my grandfather's house. Curiously, the olfactory receptor neurons that once detected the smell are long gone, replaced many times over by newer ones. How is it that the smell seems so familiar, and evokes such nostalgia? The answer lies in the exquisite fidelity of the neural connections, old and new, to the same tiny foci in the brain. For example, in the mouse a small fraction of olfactory receptor neurons express the P2 odorant receptor, and they are scattered within the nasal mucosa. Yet, upon reaching the olfactory bulb, the axons of these several hundred P2 neurons converge on only two of the >1 800 synaptic units, called glomeruli. Like all olfactory neurons, the P2 cells turn over at a slow rate, such that 1–2% of the population is dying at any given time. The replacement cells grow a new axon that faithfully finds one of the two correct glomeruli. However, traffic is heavy, as thousands of regenerating axons are traversing the same terrain simultaneously in search of different, but no less-specific, synaptic addresses in the bulb.