Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 May 10;91(10):4150–4154. doi: 10.1073/pnas.91.10.4150

Effects on protein synthesis produced by pairing depolarization with serotonin, an analogue of associative learning in Aplysia.

F Noel 1, C Koumenis 1, M Nunez-Regueiro 1, U Raju 1, J H Byrne 1, A Eskin 1
PMCID: PMC43742  PMID: 8183885

Abstract

A form of associative plasticity in Aplysia, activity-dependent neuromodulation, involves the convergence of neuronal activity and the effects of a modulatory transmitter. To investigate the role of protein synthesis in associative plasticity, we examined the effects of a biochemical analogue of activity-dependent neuromodulation on the level of incorporation of labeled amino acid into proteins. To mimic associative training, abdominal ganglia were exposed to paired treatments of a depolarizing agent, elevated potassium, and a modulatory transmitter, serotonin. The effects of elevated potassium and serotonin applied alone were also examined. At least two proteins (nos. 9 and 17) were affected in a nonadditive way by the paired procedure. Incorporation of label into protein 9 was increased by the paired procedure but was not affected by either elevated potassium or serotonin. Incorporation of label into protein 17 was significantly affected by elevated potassium or serotonin, but the effect of the paired procedure was significantly less than the summed effects of elevated potassium and serotonin applied alone. These results indicate that changes in protein synthesis may be important in the induction of associative plasticities. Amino acid sequences of two peptides derived from protein 9 were obtained. Then, a partial cDNA clone for protein 9 was obtained by performing PCR with degenerate primers corresponding to portions of the sequences of the two peptides. The sequence of protein 9 is related to sequences previously reported for a family of genes comprising the stringent starvation protein of Escherichia coli, auxin-induced proteins of plants, and glutathione S-transferases of a number of organisms.

Full text

PDF
4150

Images in this article

4152Image
on p.4152
4153Image
on p.4153
4153Image
on p.4153

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abraham W. C., Dragunow M., Tate W. P. The role of immediate early genes in the stabilization of long-term potentiation. Mol Neurobiol. 1991;5(2-4):297–314. doi: 10.1007/BF02935553. [DOI] [PubMed] [Google Scholar]
  2. Abrams T. W., Kandel E. R. Is contiguity detection in classical conditioning a system or a cellular property? Learning in Aplysia suggests a possible molecular site. Trends Neurosci. 1988 Apr;11(4):128–135. doi: 10.1016/0166-2236(88)90137-3. [DOI] [PubMed] [Google Scholar]
  3. Abrams T. W., Karl K. A., Kandel E. R. Biochemical studies of stimulus convergence during classical conditioning in Aplysia: dual regulation of adenylate cyclase by Ca2+/calmodulin and transmitter. J Neurosci. 1991 Sep;11(9):2655–2665. doi: 10.1523/JNEUROSCI.11-09-02655.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  5. Andrade R. Enhancement of beta-adrenergic responses by Gi-linked receptors in rat hippocampus. Neuron. 1993 Jan;10(1):83–88. doi: 10.1016/0896-6273(93)90244-l. [DOI] [PubMed] [Google Scholar]
  6. Barzilai A., Kennedy T. E., Sweatt J. D., Kandel E. R. 5-HT modulates protein synthesis and the expression of specific proteins during long-term facilitation in Aplysia sensory neurons. Neuron. 1989 Jun;2(6):1577–1586. doi: 10.1016/0896-6273(89)90046-9. [DOI] [PubMed] [Google Scholar]
  7. Bliss T. V., Collingridge G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993 Jan 7;361(6407):31–39. doi: 10.1038/361031a0. [DOI] [PubMed] [Google Scholar]
  8. Bourne H. R., Nicoll R. Molecular machines integrate coincident synaptic signals. Cell. 1993 Jan;72 (Suppl):65–75. doi: 10.1016/s0092-8674(05)80029-7. [DOI] [PubMed] [Google Scholar]
  9. Buonomano D. V., Byrne J. H. Long-term synaptic changes produced by a cellular analog of classical conditioning in Aplysia. Science. 1990 Jul 27;249(4967):420–423. doi: 10.1126/science.2165631. [DOI] [PubMed] [Google Scholar]
  10. Byrne J. H. Cellular analysis of associative learning. Physiol Rev. 1987 Apr;67(2):329–439. doi: 10.1152/physrev.1987.67.2.329. [DOI] [PubMed] [Google Scholar]
  11. Byrne J. H., Zwartjes R., Homayouni R., Critz S. D., Eskin A. Roles of second messenger pathways in neuronal plasticity and in learning and memory. Insights gained from Aplysia. Adv Second Messenger Phosphoprotein Res. 1993;27:47–108. [PubMed] [Google Scholar]
  12. Carpenter D. O., Alving B. O. A contribution of an electrogenic Na+ pump to membrane potential in Aplysia neurons. J Gen Physiol. 1968 Jul;52(1):1–21. doi: 10.1085/jgp.52.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Castellucci V. F., Kennedy T. E., Kandel E. R., Goelet P. A quantitative analysis of 2-D gels identifies proteins in which labeling is increased following long-term sensitization in Aplysia. Neuron. 1988 Jun;1(4):321–328. doi: 10.1016/0896-6273(88)90080-3. [DOI] [PubMed] [Google Scholar]
  14. Crow T., Forrester J. Inhibition of protein synthesis blocks long-term enhancement of generator potentials produced by one-trial in vivo conditioning in Hermissenda. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4490–4494. doi: 10.1073/pnas.87.12.4490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Davis H. P., Squire L. R. Protein synthesis and memory: a review. Psychol Bull. 1984 Nov;96(3):518–559. [PubMed] [Google Scholar]
  16. Dominov J. A., Stenzler L., Lee S., Schwarz J. J., Leisner S., Howell S. H. Cytokinins and auxins control the expression of a gene in Nicotiana plumbaginifolia cells by feedback regulation. Plant Cell. 1992 Apr;4(4):451–461. doi: 10.1105/tpc.4.4.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Eskin A., Garcia K. S., Byrne J. H. Information storage in the nervous system of Aplysia: specific proteins affected by serotonin and cAMP. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2458–2462. doi: 10.1073/pnas.86.7.2458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ginty D. D., Bading H., Greenberg M. E. Trans-synaptic regulation of gene expression. Curr Opin Neurobiol. 1992 Jun;2(3):312–316. doi: 10.1016/0959-4388(92)90121-z. [DOI] [PubMed] [Google Scholar]
  19. Glanzman D. L., Kandel E. R., Schacher S. Target-dependent structural changes accompanying long-term synaptic facilitation in Aplysia neurons. Science. 1990 Aug 17;249(4970):799–802. doi: 10.1126/science.2389145. [DOI] [PubMed] [Google Scholar]
  20. Glanzman D. L., Mackey S. L., Hawkins R. D., Dyke A. M., Lloyd P. E., Kandel E. R. Depletion of serotonin in the nervous system of Aplysia reduces the behavioral enhancement of gill withdrawal as well as the heterosynaptic facilitation produced by tail shock. J Neurosci. 1989 Dec;9(12):4200–4213. doi: 10.1523/JNEUROSCI.09-12-04200.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gorman A. L., Marmor M. F. Contributions of the sodium pump and ionic gradients to the membrane potential of a molluscan neurone. J Physiol. 1970 Nov;210(4):897–917. doi: 10.1113/jphysiol.1970.sp009248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. HODGKIN A. L., KEYNES R. D. The potassium permeability of a giant nerve fibre. J Physiol. 1955 Apr 28;128(1):61–88. doi: 10.1113/jphysiol.1955.sp005291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hawkins R. D., Abrams T. W., Carew T. J., Kandel E. R. A cellular mechanism of classical conditioning in Aplysia: activity-dependent amplification of presynaptic facilitation. Science. 1983 Jan 28;219(4583):400–405. doi: 10.1126/science.6294833. [DOI] [PubMed] [Google Scholar]
  24. Hawkins R. D., Kandel E. R., Siegelbaum S. A. Learning to modulate transmitter release: themes and variations in synaptic plasticity. Annu Rev Neurosci. 1993;16:625–665. doi: 10.1146/annurev.ne.16.030193.003205. [DOI] [PubMed] [Google Scholar]
  25. Ishihama A., Saitoh T. Subunits of RNA polymerase in function and structure. IX. Regulation of RNA polymerase activity by stringent starvation protein (SSP). J Mol Biol. 1979 Apr 25;129(4):517–530. doi: 10.1016/0022-2836(79)90466-2. [DOI] [PubMed] [Google Scholar]
  26. Kandel E. R., Abrams T., Bernier L., Carew T. J., Hawkins R. D., Schwartz J. H. Classical conditioning and sensitization share aspects of the same molecular cascade in Aplysia. Cold Spring Harb Symp Quant Biol. 1983;48(Pt 2):821–830. doi: 10.1101/sqb.1983.048.01.085. [DOI] [PubMed] [Google Scholar]
  27. Kennedy T. E., Gawinowicz M. A., Barzilai A., Kandel E. R., Sweatt J. D. Sequencing of proteins from two-dimensional gels by using in situ digestion and transfer of peptides to polyvinylidene difluoride membranes: application to proteins associated with sensitization in Aplysia. Proc Natl Acad Sci U S A. 1988 Sep;85(18):7008–7012. doi: 10.1073/pnas.85.18.7008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kennedy T. E., Kuhl D., Barzilai A., Sweatt J. D., Kandel E. R. Long-term sensitization training in Aplysia leads to an increase in calreticulin, a major presynaptic calcium-binding protein. Neuron. 1992 Dec;9(6):1013–1024. doi: 10.1016/0896-6273(92)90062-i. [DOI] [PubMed] [Google Scholar]
  29. Kerkut G. A., Meech R. W. The effect of ions on the membrane potential of snail neurones. Comp Biochem Physiol. 1967 Feb;20(2):411–429. doi: 10.1016/0010-406x(67)90257-5. [DOI] [PubMed] [Google Scholar]
  30. Meyer R. C., Jr, Goldsbrough P. B., Woodson W. R. An ethylene-responsive flower senescence-related gene from carnation encodes a protein homologous to glutathione S-transferases. Plant Mol Biol. 1991 Aug;17(2):277–281. doi: 10.1007/BF00039505. [DOI] [PubMed] [Google Scholar]
  31. Montarolo P. G., Goelet P., Castellucci V. F., Morgan J., Kandel E. R., Schacher S. A critical period for macromolecular synthesis in long-term heterosynaptic facilitation in Aplysia. Science. 1986 Dec 5;234(4781):1249–1254. doi: 10.1126/science.3775383. [DOI] [PubMed] [Google Scholar]
  32. Noel F., Nuñez-Regueiro M., Cook R., Byrne J. H., Eskin A. Long-term changes in synthesis of intermediate filament protein, actin and other proteins in pleural sensory neurons of Aplysia produced by an in vitro analogue of sensitization training. Brain Res Mol Brain Res. 1993 Aug;19(3):203–210. doi: 10.1016/0169-328x(93)90027-m. [DOI] [PubMed] [Google Scholar]
  33. Noel F., Scholz K. P., Eskin A., Byrne J. H. Common set of proteins in Aplysia sensory neurons affected by an in vitro analogue of long-term sensitization training, 5-HT and cAMP. Brain Res. 1991 Dec 24;568(1-2):67–75. doi: 10.1016/0006-8993(91)91380-j. [DOI] [PubMed] [Google Scholar]
  34. Ocorr K. A., Walters E. T., Byrne J. H. Associative conditioning analog selectively increases cAMP levels of tail sensory neurons in Aplysia. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2548–2552. doi: 10.1073/pnas.82.8.2548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pickett C. B., Lu A. Y. Glutathione S-transferases: gene structure, regulation, and biological function. Annu Rev Biochem. 1989;58:743–764. doi: 10.1146/annurev.bi.58.070189.003523. [DOI] [PubMed] [Google Scholar]
  36. Raju U., Nunez-Regueiro M., Cook R., Kaetzel M. A., Yeung S. C., Eskin A. Identification of an annexin-like protein and its possible role in the Aplysia eye circadian system. J Neurochem. 1993 Oct;61(4):1236–1245. doi: 10.1111/j.1471-4159.1993.tb13614.x. [DOI] [PubMed] [Google Scholar]
  37. Rose S. P. How chicks make memories: the cellular cascade from c-fos to dendritic remodelling. Trends Neurosci. 1991 Sep;14(9):390–397. doi: 10.1016/0166-2236(91)90027-r. [DOI] [PubMed] [Google Scholar]
  38. Serizawa H., Fukuda R. Structure of the gene for the stringent starvation protein of Escherichia coli. Nucleic Acids Res. 1987 Feb 11;15(3):1153–1163. doi: 10.1093/nar/15.3.1153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sheng M., McFadden G., Greenberg M. E. Membrane depolarization and calcium induce c-fos transcription via phosphorylation of transcription factor CREB. Neuron. 1990 Apr;4(4):571–582. doi: 10.1016/0896-6273(90)90115-v. [DOI] [PubMed] [Google Scholar]
  40. Sulston J., Du Z., Thomas K., Wilson R., Hillier L., Staden R., Halloran N., Green P., Thierry-Mieg J., Qiu L. The C. elegans genome sequencing project: a beginning. Nature. 1992 Mar 5;356(6364):37–41. doi: 10.1038/356037a0. [DOI] [PubMed] [Google Scholar]
  41. Sweatt J. D., Kandel E. R. Persistent and transcriptionally-dependent increase in protein phosphorylation in long-term facilitation of Aplysia sensory neurons. Nature. 1989 May 4;339(6219):51–54. doi: 10.1038/339051a0. [DOI] [PubMed] [Google Scholar]
  42. Toung Y. P., Tu C. P. Drosophila glutathione S-transferases have sequence homology to the stringent starvation protein of Escherichia coli. Biochem Biophys Res Commun. 1992 Jan 15;182(1):355–360. doi: 10.1016/s0006-291x(05)80152-4. [DOI] [PubMed] [Google Scholar]
  43. Walters E. T., Byrne J. H. Associative conditioning of single sensory neurons suggests a cellular mechanism for learning. Science. 1983 Jan 28;219(4583):405–408. doi: 10.1126/science.6294834. [DOI] [PubMed] [Google Scholar]
  44. van der Zaal E. J., Droog F. N., Boot C. J., Hensgens L. A., Hoge J. H., Schilperoort R. A., Libbenga K. R. Promoters of auxin-induced genes from tobacco can lead to auxin-inducible and root tip-specific expression. Plant Mol Biol. 1991 Jun;16(6):983–998. doi: 10.1007/BF00016071. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES