§ ERATO, Yamamoto Behavior Genes Project at Mitsubishi-Kasei Institute of Life Sciences, 11 Minami-Ooya, Machida-shi, 194 Tokyo, Japan, ~ Cold Spring Harbor Laboratory, P. O. Box 100, Cold Spring Harbor, New York 11724, U.S.A.,
fickle was isolated as a P-element induced mutation in which the copulatory span is highly variable and repetitive copulation in mated pairs often occurs soon after separation. The sequence of cDNA for the putative fickle gene is similar to that of Dsrc28C and it shows extensive homology with the Itk (interleukin-2-inducible T-cell kinase) and Btk (Bruton's tyrosine kinase) genes. We examined if the fickle kinase plays any role in non-associative learning of the jump reflex, an escape response. During habituation, a single fly is exposed to repetitive aversive odor pulses. Initially, flies show rigorous responses to the odor cues, but these response wane over repeated trials. Habituation in fickle mutants is significantly faster than that of wild-type flies. Importantly, the initial jump, spontaneous recovery and dishabituation levels did not differ significantly between fickle and wild-type flies. The jump response was also sensitized by exposing naive flies to strong mechanical shaking and then measuring jump responses to a single odor stimulus. In contrast to wild-type flies, fickle mutants failed to show any sensitization. These data suggest the involvement of a Btk-like tyrosine-kinase in behavioral plasticity. We demonstrate that fickle has a specific defect in sensitization which leads to fast habituation. Moreover, the fickle mutant unequivocally differentiates sensitization from dishabituation, suggesting that the former is dependent on a Btk-like tyrosine-kinase and the latter relies upon a distinct molecular mechanism.