The ability for organisms to sense and respond to changes in the environment is crucial for survival. Monitoring the activity of all neurons facilitates an integrated response of the nervous system enabling rapid changes in behavior. We have identified a system where neuropeptide expression is dependent on the ability of the BAG neurons to sense carbon dioxide. In C. elegans, CO2 sensing is mediated through the receptor-type guanylate cyclase GCY-9 that is expressed exclusively in the BAG neurons. GCY-9 binding to CO2 leads to accumulation of cGMP, thereby opening the calcium channel TAX-2/TAX-4. Subsequent calcium influx provokes an integrated downstream cascade that enables the worm to change direction away from high CO2.
How the activity of the BAG neurons regulates expression of downstream factors is poorly understood. We found that expression of the FMRF-amide FLP-19 neuropeptide is exquisitely sensitive to the ability for worms to sense CO2. Mutation of gcy-9 or tax-4 results in loss of flp-19 expression in the BAG neurons This defect is specific for the CO2 sensing capability of the BAG neurons, as mutants with impaired oxygen sensing exhibit wild type expression of flp-19. What are the molecular mechanisms that control this plasticity? We found that the expression of flp-19 in BAGs is controlled by the activity-dependent transcription factor CREB (CRH-1) through a kinase cascade. This pathway involves the calmodulin-dependant kinase CamKII (UNC-43) and the PKA (KIN-2) signaling pathway. We have therefore shown for the first time that neuropeptide gene expression in the BAG sensory neurons is modulated by the ability to sense changes in carbon dioxide.
We believe that expression of flp-19 reflects the activity of the BAG neurons and that FLP-19 regulates aspects of BAG-mediated behavioral responses. We expect that our findings will yield insights into the molecular mechanisms that underlie neuropeptide expression in sensory neurons and those that control neuronal plasticity.
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