A protein once thought to be a principal player in linking nerve responses in the nose to those in the brain actually has a more specialized role, according to a Yale School of Medicine study published in Molecular and Cellular Neuroscience.
Neurons in the nose express 1,000 different receptors that detect incoming smells. Axon extensions from these sensory neurons converge into the brain's olfactory bulb, where they form a structure called a glomerulus. Odor information is then relayed to many regions throughout the brain.
The protein olfactory cell adhesion molecule (OCAM) was long thought to be involved in the growth and targeting of axons to the olfactory bulb. This study reports that the protein is more important for coordinating neural connections within the glomeruli.
Glomeruli are normally separated into two compartments. In one compartment, incoming olfactory (sensory) axons connect with projection neurons that connect with higher cortical regions in the brain. In the second compartment, the incoming axons connect to interneurons and then modulate the projection neurons.
In mice engineered without OCAM the two compartments were no longer defined and the different types of connections were intermixed, according to Charles Greer, professor in the Departments of Neurobiology and Neurosurgery and an author of the study. The researchers speculate that the compartmentalization of these synaptic circuits within glomeruli may help to coordinate their activity.
Although mice bred without OCAM have a better sense of smell and could detect a very low concentration of an odor, "we theorize that they may not be able to discriminate between odors," Greer said.
He said the next step will be to test whether OCAM is responsible for the compartmentalization in the glomeruli. "We have shown that the absence of OCAM disrupts the compartmental organization within the glomeruli, however, we do not yet know why it does so. We need to understand the mechanisms via which OCAM exerts its effects."
Co-authors include Andreas Walz and Peter Mombaerts of Rockefeller University and Helen Treloar of Yale. The research was supported in part by the National Institutes of Health.
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