SUMMARY Sensory adaptation represents a form of experience-dependent plasticity that allows neurons to retain high sensitivity over a broad dynamic range. The mechanisms by which sensory neuron responses are altered on different timescales during adaptation are unclear. The threshold for temperature-evoked activity in the AFD thermosensory neurons (T*AFD) in C. elegans is set by the cultivation temperature (Tc), and regulated by intracellular cGMP levels. We find that T*AFD adapts on both short and long timescales upon exposure to temperatures warmer than Tc, and that prolonged exposure to warmer temperatures alters expression of AFD-specific receptor guanylyl cyclase genes. These temperature-regulated changes in gene expression are mediated by the CMK-1 CaMKI enzyme which exhibits Tc-dependent nucleocytoplasmic shuttling in AFD. Our results indicate that CaMKI-mediated changes in sensory gene expression contribute to long-term adaptation of T*AFD, and suggest that similar temporally and mechanistically distinct phases may regulate the operating ranges of other sensory neurons.

Summary The lung harbors its basal stem/progenitor cells (BSCs) in the protected environment of the cartilaginous airways. After major lung injuries, BSCs are activated and recruited to sites of injury. Here, we show that during homeostasis, BSCs in cartilaginous airways maintain their stem cell state by down-regulating the Hippo pathway (resulting in increased nuclear Yap), which generates a localized Fgf10 expressing stromal niche; in contrast, differentiated epithelial cells in non-cartilaginous airways maintain quiescence by activating the Hippo pathway and inhibiting Fgf10 expression in airway smooth muscle cells (ASMCs). However, upon injury, surviving differentiated epithelial cells spread to maintain barrier function and recruit integrin linked kinase to adhesion sites, which leads to Merlin degradation, down-regulation of the Hippo pathway, nuclear Yap translocation and expression and secretion of Wnt7b. Epithelial-derived Wnt7b, then in turn, induces Fgf10 expression in ASMCs which extends the BSC niche to promote regeneration.

SUMMARY Thermosensation is critical for optimal regulation of physiology and behavior. C. elegans acclimates to its cultivation temperature (Tc), and exhibits thermosensitive behaviors at temperatures relative to Tc. These behaviors are mediated primarily by the AFD sensory neurons which are extraordinarily thermosensitive, and respond to thermal fluctuations at temperatures above a Tc-determined threshold. Although cGMP signaling is necessary for thermotransduction, the thermosensors in AFD are unknown. Here we show that AFD-specific receptor guanylyl cyclases (rGCs) are instructive for thermosensation. In addition to being necessary for thermotransduction, ectopic expression of these rGCs confers highly temperature-dependent responses onto diverse cell types. We find that the temperature response threshold is determined by the rGC and cellular context, and that multiple domains contribute to their thermosensory properties. Identification of thermosensory rGCs in C. elegans provides insight into mechanisms of thermosensation and thermal acclimation, and suggests that rGCs may represent a new family of molecular thermosensors.

SUMMARY Through encounters with predators, competitors, and noxious stimuli, animals have evolved defensive responses that minimize injury and are essential for survival. Physiological adaptation modulates the stimulus intensities that trigger such nocifensive behaviors, but the molecular networks that define their operating range are largely unknown. Here, we identify a novel, gain-of-function allele of the cmk-1 CaMKI gene in C. elegans and show that loss of the regulatory domain of the CaMKI enzyme produces thermal analgesia and shifts the operating range for nocifensive heat avoidance to higher temperatures. Such analgesia depends on nuclear CMK-1 signaling, while cytoplasmic CMK-1 signaling lowers the threshold for thermal avoidance. CMK-1 acts downstream of heat detection in thermal receptor neurons and controls neuropeptide release. Our results establish CaMKI as a key regulator of the operating range for nocifensive behaviors, and suggest strategies for producing thermal analgesia through the regulation of CaMKI-dependent signaling.

SUMMARY Background The neuronal mechanisms that encode specific stimulus features in order to elicit defined behavioral responses are poorly understood. C. elegans forms a memory of its cultivation temperature (Tc) and exhibits distinct behaviors in different temperature ranges relative to Tc. In particular, C. elegans tracks isotherms only in a narrow temperature band near Tc. Tc memory is in part encoded by the threshold of responsiveness (T*AFD) of the AFD thermosensory neuron pair to temperature stimuli. However, since AFD thermosensory responses appear to be similar at all examined temperatures above T*AFD, the mechanisms that generate specific behaviors in defined temperature ranges remain to be determined. Results Here, we show that the AFD neurons respond to the sinusoidal variations in thermal stimuli followed by animals during isothermal tracking (IT) behavior only in a narrow temperature range near Tc. We find that mutations in the AFD-expressed gcy-8 receptor guanylyl cyclase (rGC) gene result in defects in the execution of IT behavior, and are associated with defects in the responses of the AFD neurons to oscillating thermal stimuli. In contrast, mutations in the gcy-18 or gcy-23 rGCs alter the temperature range in which IT behavior is exhibited. Alteration of intracellular cGMP levels via rGC mutations or addition of cGMP analogs shift the lower and upper ranges of the temperature range of IT behavior in part via alteration in T*AFD. Conclusions Our observations provide insights into the mechanisms by which a single sensory neuron type encodes features of a given stimulus to generate different behaviors in defined zones.