We previously showed that calcineurin TAX-6 negatively regulates sensitivity of sensory neurons in C. elegans (1). A growing number of studies have been accumulated for the role of calcineurin on learning and memory, such as induction of LTP and LTM in mammalian hippocampus, although the underlying molecular and cellular mechanisms are still unclear. We attempted to investigate the function of calcineurin in the aspect of learning and memory in C. elegans. While tax-6 gene is expressed in sensory neurions, it is also expressed in nearly all interneurons, where the learning and memory processes should occur. To pursue our study, we employed an associative learning paradigm with temperature and starvation (Aho assay) (2). Also, we made use of tax-6(lf); Ex[pAK2] strain. Since pAK2, a short promoter of tax-6, drives TAX-6 expression only in sensory neurons, it is likely that interneurons remain to be defective in tax-6(lf); Ex[pAK2] strain. The expression of tax-6 gene under the control of pAK2 is enough to rescue abnormal sensory behaviors of tax-6(lf) mutants (1).Well-fed tax-6(lf); Ex[pAK2] animals migrated to the cultivation temperature on a temperature gradient as seen in well-fed wild type animals. We found that tax-6(lf); Ex[pAK2] animals did not avoid the cultivation temperature after cultivated in starved condition at 17C. This Aho phenotype was rescued by pan-neuronal expression of tax-6 cDNA using unc-14 promoter. tax-6(lf);Ex[pAK2] animals however normally avoided conditioned temperature after cultivation at 23C. These results suggest that there are temperature dependent mechanisms of starvation-induced neural plasticity in thermotaxis (3). To identify interneuron(s) defective in tax-6(lf); Ex[pAK2] animals to cause Aho phenotype at 17C, tax-6 cDNA was expressed in subsets of interneurons in tax-6(lf); Ex[pAK2] animals. The expressions of TAX-6 driven by either one of three promoters, glr-3, lin-11 and unc-86, partially rescued the Aho phenotype. Intriguingly, these promoters allow TAX-6 expressions in two interneurons that are essential components of thermotaxis circuit (4): glr-3 promoter drives the expression in RIA, and both lin-11 and unc-86 promoters drive the expression in AIZ. Altogether, Aho phenotype is thus caused by abnormal function of both RIA and AIZ interneurons and calcineurin is normally required for these two interneurons to execute normal starvation-induced neural plasticity of thermotaxis.(1) Kuhara et. al., 2002, Neuron 33, 751. (2) Mohri et.al., 2003, IWM abstract. (3) Nishio et. al. 2003, IWM abstract. (4) Mori and Ohshima, 1995, Nature 376, 344.