Cyclic-nucleotides play an important role in the mechanism of learning and memory. For example, rutabaga and dunce mutants in Drosophila are defective in electric shock-induced odorant avoidance; rutabaga and dunce genes encode adenylyl cyclase and cAMP specific phosphodiesterase, a homologue of mammalian phosphodiesterase 4 (PDE4), respectively (1). In the Lymnaea associative learning paradigm with amyl-acetate and feeding, animals treated with inhibitors of the nitric oxide-cGMP signaling pathway are defective in amyl-acetate-induced feeding responses (2). C. elegans has six predicted genes that encode homologues of mammalian PDEs. We designated these genes
pde-1, -2, -3, -4, -5 and -6, which correspond to PDE1, 2, 3, 4, 10 and 8, respectively. To investigate the role of cyclic-nucleotide in learning and memory of C. elegans, we utilized starvation-induced cultivation temperature avoidance (Aho assay) as a behavioral paradigm (see abstract by Mohri et al.). We assayed cultivation temperature avoidance for
pde-5(
nj49) and
egl-4(
n479).
pde-5 (C32E12.2) encodes a homologue of PDE10 that is known as cAMP-inhibited cGMP PDE (3), and
egl-4 encodes cGMP dependent protein kinase (4). To analyze the effect of cultivation conditions during development, these mutants were grown differently with different temperatures before testing. They were cultured at 17, 20 or 25C from hatching to L4 larval stage and then cultured at either 17 or 25C till the adulthood. The
pde-5(
nj49) mutant, a TMP/UV-induced deletion mutant, showed weak Aho phenotype after cultivation at 17C as well as at 25C from L4 larval stage. The
egl-4(
n479) null mutant (5) showed very severe Aho phenotype after cultivation at 25C from L4 larval stage, but this mutant showed almost normal cultivation temperature avoidance after cultivation at 17C from L4 larval stage. These result suggest that PDE-5 and EGL-4 are essential for mechanism of cultivation temperature avoidance, namely one form of learning and memory in C. elegans. Perhaps, separated systems may function in low (17C) and high (25C) temperature memory formations and EGL-4 may be involved in only one of the system (25C). We will continue to analyze
pde-5(
nj49) and
egl-4(
n479) using other learning paradigms and will assay cultivation temperature avoidance of other pde null mutants. (1) Dudai, 1989, The Neurobiology of Memory. (2) Kemenes et al., 2002, J. Neurosci. 22, 1414. (3)Soderling and Beavo, 2000, Current Opinion in Cell Biol. 12, 174. (4) Stansberry et al., 2001, J. Neurochem. 76, 1177. (5) Fujiwara et al., 2002, Neuron 36, 1091.