Abstract
Genetic dissection of learning and memory in Drosophila has been limited by the existence of ethyl methanesulfonate (EMS)-induced mutations in only a small number of X-linked genes. To remedy this shortcoming, we have begun a P element mutagenesis to screen for autosomal mutations that disrupt associative learning and/or memory. The generation of ``P-tagged'' mutant alleles will expedite molecular cloning of these new genes. Here, we describe a behavior-genetic characterization of latheo(P1), a recessive, hypomorphic mutation of an essential gene. latheo(P1) flies perform poorly in olfactory avoidance conditioning experiments. This performance deficit could not be attributed to abnormal olfactory acuity or shock reactivity-two task-relevant ``peripheral'' behaviors which are used during classical conditioning. Thus, the latheo(P1) mutation appears to affect learning/memory specifically. Consistent with chromosomal in situ localization of the P element insertion, deficiencies of the 49F region of the second chromosome failed to complement the behavioral effect of the latheo(P1) mutation. Further complementation analyses between latheo(P1) and lethal alleles, produced by excision of the latheo(P1) insert or by EMS or γ-rays, in the 49F region mapped the latheo mutation to one vital complementation group. Flies heterozygous for latheo(P1) and one of two EMS lethal alleles or one lethal excision allele also show the behavioral deficits, thereby demonstrating that the behavioral and lethal phenotypes co-map to the same locus.
Full Text
The Full Text of this article is available as a PDF (6.6 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aceves-Piña E. O., Quinn W. G. Learning in normal and mutant Drosophila larvae. Science. 1979 Oct 5;206(4414):93–96. doi: 10.1126/science.206.4414.93. [DOI] [PubMed] [Google Scholar]
- Bellen H. J., Gregory B. K., Olsson C. L., Kiger J. A., Jr Two Drosophila learning mutants, dunce and rutabaga, provide evidence of a maternal role for cAMP on embryogenesis. Dev Biol. 1987 Jun;121(2):432–444. doi: 10.1016/0012-1606(87)90180-1. [DOI] [PubMed] [Google Scholar]
- Bellen H. J., Kiger J. A., Jr Sexual hyperactivity and reduced longevity of dunce females of Drosophila melanogaster. Genetics. 1987 Jan;115(1):153–160. doi: 10.1093/genetics/115.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benzer S. BEHAVIORAL MUTANTS OF Drosophila ISOLATED BY COUNTERCURRENT DISTRIBUTION. Proc Natl Acad Sci U S A. 1967 Sep;58(3):1112–1119. doi: 10.1073/pnas.58.3.1112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Booker R., Quinn W. G. Conditioning of leg position in normal and mutant Drosophila. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3940–3944. doi: 10.1073/pnas.78.6.3940. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brunner A., Wolf R., Pflugfelder G. O., Poeck B., Heisenberg M. Mutations in the proximal region of the optomotor-blind locus of Drosophila melanogaster reveal a gradient of neuroanatomical and behavioral phenotypes. J Neurogenet. 1992 Feb;8(1):43–55. doi: 10.3109/01677069209167271. [DOI] [PubMed] [Google Scholar]
- Byers D., Davis R. L., Kiger J. A., Jr Defect in cyclic AMP phosphodiesterase due to the dunce mutation of learning in Drosophila melanogaster. Nature. 1981 Jan 1;289(5793):79–81. doi: 10.1038/289079a0. [DOI] [PubMed] [Google Scholar]
- Campos A. R., Grossman D., White K. Mutant alleles at the locus elav in Drosophila melanogaster lead to nervous system defects. A developmental-genetic analysis. J Neurogenet. 1985 Jun;2(3):197–218. doi: 10.3109/01677068509100150. [DOI] [PubMed] [Google Scholar]
- Chen C. N., Denome S., Davis R. L. Molecular analysis of cDNA clones and the corresponding genomic coding sequences of the Drosophila dunce+ gene, the structural gene for cAMP phosphodiesterase. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9313–9317. doi: 10.1073/pnas.83.24.9313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Choi K. W., Smith R. F., Buratowski R. M., Quinn W. G. Deficient protein kinase C activity in turnip, a Drosophila learning mutant. J Biol Chem. 1991 Aug 25;266(24):15999–15606. [PubMed] [Google Scholar]
- Coen D. P element regulatory products enhance zeste repression of a P[white duplicated] transgene in Drosophila melanogaster. Genetics. 1990 Dec;126(4):949–960. doi: 10.1093/genetics/126.4.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cooley L., Kelley R., Spradling A. Insertional mutagenesis of the Drosophila genome with single P elements. Science. 1988 Mar 4;239(4844):1121–1128. doi: 10.1126/science.2830671. [DOI] [PubMed] [Google Scholar]
- Corfas G., Dudai Y. Habituation and dishabituation of a cleaning reflex in normal and mutant Drosophila. J Neurosci. 1989 Jan;9(1):56–62. doi: 10.1523/JNEUROSCI.09-01-00056.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis R. L., Davidson N. Isolation of the Drosophila melanogaster dunce chromosomal region and recombinational mapping of dunce sequences with restriction site polymorphisms as genetic markers. Mol Cell Biol. 1984 Feb;4(2):358–367. doi: 10.1128/mcb.4.2.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drain P., Folkers E., Quinn W. G. cAMP-dependent protein kinase and the disruption of learning in transgenic flies. Neuron. 1991 Jan;6(1):71–82. doi: 10.1016/0896-6273(91)90123-h. [DOI] [PubMed] [Google Scholar]
- Dudai Y., Jan Y. N., Byers D., Quinn W. G., Benzer S. dunce, a mutant of Drosophila deficient in learning. Proc Natl Acad Sci U S A. 1976 May;73(5):1684–1688. doi: 10.1073/pnas.73.5.1684. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dudai Y., Sher B., Segal D., Yovell Y. Defective responsiveness of adenylate cyclase to forskolin in the Drosophila memory mutant rutabaga. J Neurogenet. 1985 Dec;2(6):365–380. doi: 10.3109/01677068509101423. [DOI] [PubMed] [Google Scholar]
- Duerr J. S., Quinn W. G. Three Drosophila mutations that block associative learning also affect habituation and sensitization. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3646–3650. doi: 10.1073/pnas.79.11.3646. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feinstein P. G., Schrader K. A., Bakalyar H. A., Tang W. J., Krupinski J., Gilman A. G., Reed R. R. Molecular cloning and characterization of a Ca2+/calmodulin-insensitive adenylyl cyclase from rat brain. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10173–10177. doi: 10.1073/pnas.88.22.10173. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fuyama Y. Behavior genetics of olfactory responses in Drosophila. I. Olfactometry and strain differences in Drosophila melanogaster. Behav Genet. 1976 Oct;6(4):407–420. doi: 10.1007/BF01065698. [DOI] [PubMed] [Google Scholar]
- Gailey D. A., Jackson F. R., Siegel R. W. Conditioning Mutations in DROSOPHILA MELANOGASTER Affect an Experience-Dependent Behavioral Modification in Courting Males. Genetics. 1984 Apr;106(4):613–623. doi: 10.1093/genetics/106.4.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gailey D. A., Villella A., Tully T. Reassessment of the effect of biological rhythm mutations on learning in Drosophila melanogaster. J Comp Physiol A. 1991 Dec;169(6):685–697. doi: 10.1007/BF00194897. [DOI] [PubMed] [Google Scholar]
- Grigliatti T. A., Hall L., Rosenbluth R., Suzuki D. T. Temperature-sensitive mutations in Drosophila melanogaster. XIV. A selection of immobile adults. Mol Gen Genet. 1973 Jan 24;120(2):107–114. doi: 10.1007/BF00267238. [DOI] [PubMed] [Google Scholar]
- Hazelrigg T., Levis R., Rubin G. M. Transformation of white locus DNA in drosophila: dosage compensation, zeste interaction, and position effects. Cell. 1984 Feb;36(2):469–481. doi: 10.1016/0092-8674(84)90240-x. [DOI] [PubMed] [Google Scholar]
- Heisenberg M., Borst A., Wagner S., Byers D. Drosophila mushroom body mutants are deficient in olfactory learning. J Neurogenet. 1985 Feb;2(1):1–30. doi: 10.3109/01677068509100140. [DOI] [PubMed] [Google Scholar]
- Helfand S. L., Carlson J. R. Isolation and characterization of an olfactory mutant in Drosophila with a chemically specific defect. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2908–2912. doi: 10.1073/pnas.86.8.2908. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Homyk T. Behavioral Mutants of DROSOPHILA MELANOGASTER. II. Behavioral Analysis and Focus Mapping. Genetics. 1977 Sep;87(1):105–128. doi: 10.1093/genetics/87.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Homyk T., Jr, Isono K., Pak W. L. Developmental and physiological analysis of a conditional mutation affecting photoreceptor and optic lobe development in Drosophila melanogaster. J Neurogenet. 1985 Nov;2(5):309–324. doi: 10.3109/01677068509102326. [DOI] [PubMed] [Google Scholar]
- Homyk T., Jr, Szidonya J., Suzuki D. T. Behavioral mutants of Drosophila melanogaster. III. Isolation and mapping of mutations by direct visual observations of behavioral phenotypes. Mol Gen Genet. 1980;177(4):553–565. doi: 10.1007/BF00272663. [DOI] [PubMed] [Google Scholar]
- Homyk T., Sheppard D. E. Behavioral Mutants of DROSOPHILA MELANOGASTER. I. Isolation and Mapping of Mutations Which Decrease Flight Ability. Genetics. 1977 Sep;87(1):95–104. doi: 10.1093/genetics/87.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kiger J. A., Jr, Davis R. L., Salz H., Fletcher T., Bowling M. Genetic analysis of cyclic nucleotide phosphodiesterases in Drosophila melanogaster. Adv Cyclic Nucleotide Res. 1981;14:273–288. [PubMed] [Google Scholar]
- Krupinski J., Coussen F., Bakalyar H. A., Tang W. J., Feinstein P. G., Orth K., Slaughter C., Reed R. R., Gilman A. G. Adenylyl cyclase amino acid sequence: possible channel- or transporter-like structure. Science. 1989 Jun 30;244(4912):1558–1564. doi: 10.1126/science.2472670. [DOI] [PubMed] [Google Scholar]
- Kulkarni S. J., Hall J. C. Behavioral and cytogenetic analysis of the cacophony courtship song mutant and interacting genetic variants in Drosophila melanogaster. Genetics. 1987 Mar;115(3):461–475. doi: 10.1093/genetics/115.3.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kulkarni S. J., Steinlauf A. F., Hall J. C. The dissonance mutant of courtship song in Drosophila melanogaster: isolation, behavior and cytogenetics. Genetics. 1988 Feb;118(2):267–285. doi: 10.1093/genetics/118.2.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kyriacou C. P., Oldroyd M., Wood J., Sharp M., Hill M. Clock mutations alter developmental timing in Drosophila. Heredity (Edinb) 1990 Jun;64(Pt 3):395–401. doi: 10.1038/hdy.1990.50. [DOI] [PubMed] [Google Scholar]
- Lasko P. F., Pardue M. L. Studies of the genetic organization of the vestigial microregion of Drosophila melanogaster. Genetics. 1988 Oct;120(2):495–502. doi: 10.1093/genetics/120.2.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levin L. R., Han P. L., Hwang P. M., Feinstein P. G., Davis R. L., Reed R. R. The Drosophila learning and memory gene rutabaga encodes a Ca2+/Calmodulin-responsive adenylyl cyclase. Cell. 1992 Feb 7;68(3):479–489. doi: 10.1016/0092-8674(92)90185-f. [DOI] [PubMed] [Google Scholar]
- Lilly M., Carlson J. smellblind: a gene required for Drosophila olfaction. Genetics. 1990 Feb;124(2):293–302. doi: 10.1093/genetics/124.2.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lipshitz H. D., Kankel D. R. Specificity of gene action during central nervous system development in Drosophila melanogaster: analysis of the lethal (1) optic ganglion reduced locus. Dev Biol. 1985 Mar;108(1):56–77. doi: 10.1016/0012-1606(85)90009-0. [DOI] [PubMed] [Google Scholar]
- Livingstone M. S. Genetic dissection of Drosophila adenylate cyclase. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5992–5996. doi: 10.1073/pnas.82.17.5992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Livingstone M. S., Sziber P. P., Quinn W. G. Loss of calcium/calmodulin responsiveness in adenylate cyclase of rutabaga, a Drosophila learning mutant. Cell. 1984 May;37(1):205–215. doi: 10.1016/0092-8674(84)90316-7. [DOI] [PubMed] [Google Scholar]
- McKenna M., Monte P., Helfand S. L., Woodard C., Carlson J. A simple chemosensory response in Drosophila and the isolation of acj mutants in which it is affected. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8118–8122. doi: 10.1073/pnas.86.20.8118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meehan M. J., Wilson R. Locomotor activity in the Tyr-1 mutant of Drosophila melanogaster. Behav Genet. 1987 Sep;17(5):503–512. doi: 10.1007/BF01073117. [DOI] [PubMed] [Google Scholar]
- O'Kane C. J., Gehring W. J. Detection in situ of genomic regulatory elements in Drosophila. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9123–9127. doi: 10.1073/pnas.84.24.9123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pflugfelder G. O., Roth H., Poeck B., Kerscher S., Schwarz H., Jonschker B., Heisenberg M. The lethal(1)optomotor-blind gene of Drosophila melanogaster is a major organizer of optic lobe development: isolation and characterization of the gene. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1199–1203. doi: 10.1073/pnas.89.4.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robertson H. M., Preston C. R., Phillis R. W., Johnson-Schlitz D. M., Benz W. K., Engels W. R. A stable genomic source of P element transposase in Drosophila melanogaster. Genetics. 1988 Mar;118(3):461–470. doi: 10.1093/genetics/118.3.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robinow S., White K. Characterization and spatial distribution of the ELAV protein during Drosophila melanogaster development. J Neurobiol. 1991 Jul;22(5):443–461. doi: 10.1002/neu.480220503. [DOI] [PubMed] [Google Scholar]
- Shotwell S. L. Cyclic adenosine 3':5'-monophosphate phosphodiesterase and its role in learning in Drosophila. J Neurosci. 1983 Apr;3(4):739–747. doi: 10.1523/JNEUROSCI.03-04-00739.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siegel R. W., Hall J. C. Conditioned responses in courtship behavior of normal and mutant Drosophila. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3430–3434. doi: 10.1073/pnas.76.7.3430. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stäubli U., Faraday R., Lynch G. Pharmacological dissociation of memory: anisomycin, a protein synthesis inhibitor, and leupeptin, a protease inhibitor, block different learning tasks. Behav Neural Biol. 1985 May;43(3):287–297. doi: 10.1016/s0163-1047(85)91632-2. [DOI] [PubMed] [Google Scholar]
- Tempel B. L., Livingstone M. S., Quinn W. G. Mutations in the dopa decarboxylase gene affect learning in Drosophila. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3577–3581. doi: 10.1073/pnas.81.11.3577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thompson R. F., Spencer W. A. Habituation: a model phenomenon for the study of neuronal substrates of behavior. Psychol Rev. 1966 Jan;73(1):16–43. doi: 10.1037/h0022681. [DOI] [PubMed] [Google Scholar]
- Tully T., Boynton S., Brandes C., Dura J. M., Mihalek R., Preat T., Villella A. Genetic dissection of memory formation in Drosophila melanogaster. Cold Spring Harb Symp Quant Biol. 1990;55:203–211. doi: 10.1101/sqb.1990.055.01.022. [DOI] [PubMed] [Google Scholar]
- Tully T., Gergen J. P. Deletion mapping of the Drosophila memory mutant amnesiac. J Neurogenet. 1986 Jan;3(1):33–47. doi: 10.3109/01677068609106893. [DOI] [PubMed] [Google Scholar]
- Tully T., Quinn W. G. Classical conditioning and retention in normal and mutant Drosophila melanogaster. J Comp Physiol A. 1985 Sep;157(2):263–277. doi: 10.1007/BF01350033. [DOI] [PubMed] [Google Scholar]
- Watanabe T., Kankel D. R. Molecular cloning and analysis of l(1)ogre, a locus of Drosophila melanogaster with prominent effects on the postembryonic development of the central nervous system. Genetics. 1990 Dec;126(4):1033–1044. doi: 10.1093/genetics/126.4.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wheeler D. A., Kulkarni S. J., Gailey D. A., Hall J. C. Spectral analysis of courtship songs in behavioral mutants of Drosophila melanogaster. Behav Genet. 1989 Jul;19(4):503–528. doi: 10.1007/BF01066251. [DOI] [PubMed] [Google Scholar]
- Woodard C., Huang T., Sun H., Helfand S. L., Carlson J. Genetic analysis of olfactory behavior in Drosophila: a new screen yields the ota mutants. Genetics. 1989 Oct;123(2):315–326. doi: 10.1093/genetics/123.2.315. [DOI] [PMC free article] [PubMed] [Google Scholar]