Activity-Dependent Gene Expression in the Mammalian Olfactory Epithelium.

Activity-dependent processes are important to olfactory sensory neurons (OSNs) in several ways, such as cell survival and the specificity of axonal convergence. The identification of activity-dependent mRNAs has contributed to our understanding of OSN axon convergence, but has revealed surprisingly little about other processes. Published studies of activity-dependent mRNAs in olfactory mucosae overlap poorly, but by combining these agreements with meta-analysis of existing data we identify 443 mRNAs that respond to methods that alter OSN activity. Three hundred and fifty of them are expressed in mature OSNs, consistent with the expectation that activity-dependent responses are cell autonomous and driven by odor stimulation. Many of these mRNAs encode proteins that function at presynaptic terminals or support electrical activity, consistent with hypotheses linking activity dependence to synaptic plasticity and energy conservation. The lack of agreement between studies is due largely to underpowered experiments. In addition, methods used to alter OSN activity are susceptible to indirect or off-target effects. These effects deserve greater attention, not only to rigorously identify OSN mRNAs that respond to altered OSN activity, but also because these effects are of significant interest in their own right. For example, the mRNAs of some sustentacular cell enzymes believed to function in odorant clearance (Cyp2a4 and Cyp2g1) are sensitive to unilateral naris occlusion used to reduce odorant stimulation of the ipsilateral olfactory epithelium. Also problematic are odorant receptor mRNAs, which show little agreement across studies and are susceptible to differences in frequency of expression that masquerade as activity-dependent changes in mRNA abundance.