Temperature is an unavoidable environmental cue that affects the metabolism and behavior of any creature on Earth, yet how animals perceive temperature is poorly understood. The nematode Caenorhabditis elegans "memorizes" temperatures, and this stored information modifies its subsequent migration along a temperature gradient. We show that the olfactory neuron designated AWC senses temperature. Calcium imaging revealed that AWC responds to temperature changes and that response thresholds differ depending on the temperature to which the animal was previously exposed. In the mutant with impaired heterotrimeric guanine nucleotide-binding protein (G protein)-mediated signaling, AWC was hyperresponsive to temperature, whereas the AIY interneuron (which is postsynaptic to AWC) was hyporesponsive to temperature. Thus, temperature sensation exhibits a robust influence on a neural circuit controlling a memory-regulated behavior.

Caenorhabditis elegans exhibits a food-associated behavior that is modulated by the past cultivation temperature. Mutations in INS-1, the homolog of human insulin, caused the defect in this integrative behavior. Mutations in DAF-2/insulin receptor and AGE-1/phosphatidylinositol 3 (PI-3)-kinase partially suppressed the defect of ins-1 mutants, and a mutation in DAF-16, a forkhead-type transcriptional factor, caused a weak defect. In addition, mutations in the secretory protein HEN-1 showed synergistic effects with INS-1. Expression of AGE-1 in any of the three interneurons, AIY, AIZ, or RIA, rescued the defect characteristic of age-1 mutants. Calcium imaging revealed that starvation induced INS-1-mediated down-regulation of AIZ activity. Our results suggest that INS-1, in cooperation with HEN-1, antagonizes the DAF-2 insulin-like signaling pathway to modulate interneuron activity required for food-associated integrative behavior. The secreted peptide hormone insulin modulates neural plasticity. Insulin and insulin receptors are expressed in several regions of the rat brain (Havrankova et al. 1978a,b), insulin receptors localize to post-synapses (Abbott et al. 1999), and insulin can produce long-term depression (LTD) of synaptic transmission through endocytosis of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in rat hippocampal CA1 neurons (Man et al. 2000). In addition, Phosphatidylinositol 3 (PI-3)-kinase that functions in the insulin signaling pathway is thought to induce long-term potentiation (LTP) of synaptic transmission in the dentate gyrus of rat (Kelly and Lynch 2000). These alterations by proteins of the insulin signaling pathway may be involved in learning and memory, but what kind of behavior the insulin signaling pathway modulates has been largely unknown.The nematode Caenorhabditis elegans is well suited for the analysis of the molecular and cellular mechanisms underlying neural plasticity because of its accessible genetics, stereotyped behavioral responses, and its simple nervous system consisting of 302 neurons whose connections are entirely known (White et al. 1986). Recently, physiological analysis of the neural circuit in live worms has become possible by the use of cameleon, a genetically encodable calcium indicator, to measure Ca 2+ concentration changes (Miyawaki et al. 1997;Kimura et al. 2004).C. elegans exhibits thermotaxis, an integrative behavior in which well-fed animals in a thermal gradient are attracted to their cultivation temperature, whereas starved animals avoid it (Hedgecock and Russell 1975;Mohri et al. 2005;Rankin 2005). This food-associated behavioral plasticity, regarded the most complex behavior in C. elegans, is an ideal behavioral paradigm for comprehensive study of neural plasticity at the molecular, physiological, and behavioral levels. In this study, we show that in cooperation with a secreted protein HEN-1, an insulin homolog INS-1, and insulin-like signaling pathway modulate neuronal activity of interneurons to execute thermotaxis behavior in...

No abstract