Schild LC Zbinden L Bell HW Yu YV Sengupta P Goodman MB Glauser DA 2014 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 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. application/pdf https://sonar.ch/global/documents/93529 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuron.2014.10.039 info:eu-repo/semantics/altIdentifier/pmid/25467982 info:eu-repo/semantics/openAccess Neuron. - 2014 Adaptation, Physiological Animals Animals, Genetically Modified Avoidance Learning Caenorhabditis elegans Caenorhabditis elegans Proteins Calcium-Calmodulin-Dependent Protein Kinase Type 1 Cell Nucleolus Cytoplasm Escape Reaction Hot Temperature Mutagenesis Mutation Neurons Neuropeptides Nociception Sensory Receptor Cells Signal Transduction The balance between cytoplasmic and nuclear CaM kinase-1 signaling controls the operating range of noxious heat avoidance. http://purl.org/coar/resource_type/c_6501