Abstract
For optimal survival, animals must be able to respond robustly and flexibly to a dynamic sensory environment. Sensory systems must be able to adapt rapidly to receive and transmit relevant information in an experience and context-dependent manner. Since temperature is a key variable that informs nearly all physiological processes, thermosensory systems must maintain accurate representation of the thermosensory environment. Although much is now known about sensory transduction pathways, there are still questions unanswered about the mechanisms by which thermosensory neurons respond and adapt to changes in temperature. Using the small nematode C. elegans, I have characterized molecular mechanisms that work to maintain the high sensitivity of the thermosensory AFD neurons over a wide dynamic range. Specifically, I show that individual thermosensory guanylyl cyclases expressed in this neuron exhibit distinct modes of plasticity upon short-term temperature experience, perhaps driven by differential regulation of conserved phosphorylation sites on these proteins. I also show that there are cGMP and calcium-dependent feedback mechanisms that are integral for AFD response threshold plasticity. Upon calcium influx into the neuron, the neuronal calcium sensor NCS-2 acts to modulate basal cGMP levels through interactions with the thermosensory guanylyl cyclases. Increased cyclase activity upon upwards temperature shifts activates the cGMP-dependent protein kinases EGL-4 and PKG-2, which phosphorylate the CNG-3 α subunit to raise the cGMP threshold of the channel. My data suggest a model in which these mechanisms all act in tandem to mediate the rapid shift of the AFD response threshold upon short-term temperature experience.