Targeted ingrowth and glial relationships of olfactory receptor axons in the primary olfactory pathway of an insect.

Olfactory receptor axons in many species terminate centrally in an array of distinct glomeruli that are thought to encode the molecular features of odors. Particular molecular attributes are detected by receptor neurons widely distributed over the sensory epithelium, but these neurons then project to a small number of glomeruli in the olfactory bulb. This raises perplexing questions about olfactory axon guidance, especially how axons sort by odor specificity and how they find their appropriate targets in the brain. Taking advantage of the relative cellular simplicity of the moth antennal system, we have examined receptor axons in normally developing animals and also in preparations in which the nerve was experimentally misrouted. Just before they enter the antennal lobe, receptor axons undergo a dramatic reorganization in a discrete zone filled with glial cells. Here they shed neighbor relationships and become associated with axons that have common targets and presumably share common odor specificities. Electron microscopy revealed that the growth cones of early arriving axons travel preferentially next to glial processes. The growth cones of receptor axons were relatively simple except as they entered newly forming glomeruli. Misrouted nerves turned and ran along the surface of the brain until they reached the region of the antennal lobe. In only 6% of cases did misrouted axons enter the brain ectopically, never forming glomeruli. Our results suggest that olfactory receptor axons are attracted to the antennal lobe by soluble or surface-bound cues and sort by odor specificity by using a mechanism that may involve glial cells.