In the olfactory bulb, the firing rates and coordinated firing patterns of mitral and tufted cells encode aspects of olfactory information including odor identity and whether an odor deserves attention (odor salience). Throughout life, these firing properties can change dramatically as an animal learns. While the local circuits and centrifugal inputs modulating the output of mitral and tufted cells are reasonably well understood, there is virtually no understanding of how these cells transmit odor information to other sensory processing regions along long, myelinated axonal tracts. Axonal domains such as the axon initial segment and myelinated domains like nodes of Ranvier and the myelin sheath play a vital role in neuronal firing properties and conduction velocity, but whether they adapt to facilitate information processing in adults is not known. This proposal is comprised of two aims which seek to test the hypothesis that axonal domains change in response to neuronal activity in adult animals.
The first aim uses immunohistochemistry and electron microscopy to investigate the structure of the axon initial segments, myelin sheaths, and nodes of Ranvier in adult animals following sensory deprivation with unilateral naris occlusion, and an optogenetic version of the go-no go associative learning paradigm where mice learn to detect and odorant. I will determine whether adaptations occur following sensory deprivation and learning.
The second aim i nvestigates the physiological consequences of sensory deprivation and learning on the function of axons projecting out of the olfactory bulb. Together, these experiments seek to test the hypothesis that myelin and axonal domains adapt to sensory manipulations in adults and participate in olfactory sensory processing.
Studying axon-myelin plasticity in adults is particularly important as multiple sclerosis, the most common demyelinating disease, typically affects adults. An early sign of multiple sclerosis is a diminished sense of smell that appears to be tied to disease severity. Characterizing adult myelin plasticity in the olfactory system could lead to further work on clinical tools and manipulations to stimulate myelination and reverse progression of multiple sclerosis.