Skip to main content
Log in

Molecular Mechanism of Memory Modification

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

The present review of our own and published data proposes a hypothesis for the molecular mechanisms regulating synaptic efficiency which may underlie long-term changes in behavior and modification of memory on the reactivation. The hypotheses is based on data on role of the atypical protein kinase molecule Mζ in long-term changes in synaptic efficiency by controlling the delivery of AMPA receptors, and on data on the possible nitrosylation of these molecules by nitric oxide, which is produced in synapses when nerve cells are activated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Anokhin, K. V., Tiunova, A. A., and S. P. R. Rose, “Reminder effects – reconsolidation or retrieval deficit? Pharmacological dissection with protein synthesis inhibitors following reminder for a passive-avoidance task in young chicks,” Eur. J. Neurosci., 15, No. 11, 1759–65 (2002).

    Article  PubMed  Google Scholar 

  2. Antonov, I., Ha, T., Antonova, I., Moroz, L. L., and Hawkins, R. D., “Role of nitric oxide in classical conditioning of siphon withdrawal in Aplysia,” J. Neurosci., 27, 10,993–11,002 (2007).

    Google Scholar 

  3. Artinian, J., McGauran A.-M. T., De Jaeger, X., et al., “Protein degradation, as with protein synthesis, is required during not only long-term spatial memory consolidation but also reconsolidation,” Eur. J. Neurosci., 27, 3009–3019 (2008).

    Article  PubMed  Google Scholar 

  4. Bal, N. V. and Balaban, P. M., “Ubiquitin-dependent protein degradation is required for long-term plasticity and memory,” Neirokhimiya, 32, No. 4, 275–284 (2015).

    Google Scholar 

  5. Bal, N., Roshchin, M., Salozhin, S., and Balaban, P., “Nitric oxide upregulates proteasomal protein degradation in neurons,” Cell. Mol. Neurobiol. (2016), doi: https://doi.org/10.1007/s10571-016-0413-9.

  6. Balaban, P. M., Roshchin, M., Timoshenko, A. K., et al., “Nitric oxide is necessary for labilization of a consolidated context memory during reconsolidation in terrestrial snails,” Eur. J. Neurosci., 40, 2963–2970 (2014).

    Article  PubMed  Google Scholar 

  7. Balaban, P. M., Roshchin, M., Timoshenko, A. K., et al., “Homolog of protein kinase Mζ maintains context aversive memory and underlying long-term facilitation in terrestrial snail Helix,” Front. Cell. Neurosci., 9, 222 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Bredt, D. S., “Nitric oxide signaling specificity – the heart of the problem,” J. Cell Sci., 116, 9–15 (2003).

    Article  PubMed  CAS  Google Scholar 

  9. Cai, D., Chen, S., and Glanzman, D. L., “Postsynaptic regulation of longterm facilitation in Aplysia,” Curr. Biol., 18, 920–925 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Calabrese, V., Cornelius, C., Rizzarelli, E., et al., “Nitric oxide in cell survival: a Janus molecule,” Antioxid. Redox. Signal., 11, 2717–2739 (2009).

    Article  PubMed  CAS  Google Scholar 

  11. Christopherson, K. S. and Bredt, D. S., “Nitric oxide in excitable tissues: physiological roles and disease,” J. Clin. Invest., 100, 2424–2429 (1997).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Debiec, J., LeDoux, J. E., and Nader K., “Cellular and systems reconsolidation in the hippocampus,” Neuron, 36, 527–538 (2002).

    Article  PubMed  CAS  Google Scholar 

  13. Duvarci, S. and Nader, K., “Characterization of fear memory reconsolidation,” J. Neurosci., 24, 9269–9275 (2004).

    Article  PubMed  CAS  Google Scholar 

  14. Duvarci, S., C. B. Mamou, and Nader, K., “Extinction is not a sufficient condition to prevent fear memories from undergoing reconsolidation in the basolateral amygdala,” Eur. J. Neurosci., 24, 249–260 (2006).

    Article  PubMed  Google Scholar 

  15. Duvarci, S., Nader, K., and LeDoux, J. E., “De novo mRNA synthesis is required for both consolidation and re-consolidation of fear memories in the amygdala,” Learn. Mem., 15, 747–755 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Eisenberg, M., Kobilo, T., Berman, D. E., and Dudai, Y., “Stability of retrieved memory: inverse correlation with trace dominance,” Science, 301, 1102–1104 (2003).

    Article  PubMed  CAS  Google Scholar 

  17. Evuarherhe, O., Barker, G. R. I., Savalli, G., et al., “Early memory formation disrupted by atypical PKC inhibitor ZIP in the medial prefrontal cortex but not hippocampus,” Hippocampus, 24, 934–942 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Fedele, E. and Raiteri, M., “In vivo studies of the cerebral glutamate receptor/NO/cGMP pathway,” Prog. Neurobiol., 58, 89–120 (1999).

    Article  PubMed  CAS  Google Scholar 

  19. Gainutdinova, T. H., Tagirova, R. R., Ismailova, A. I., et al., “Reconsolidation of a context long-term memory in the terrestrial snail requires protein synthesis,” Learn. Mem., 12, 620–625 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gelbard-Sagiv, H., Mukamel, R., Harel, M., et al., “Internally generated reactivation of single neurons in human hippocampus during free recall,” Science, 322, 96–101 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Hawkins, R. D., Son, H., and Arancio, O., “Nitric oxide as a retrograde messenger during long-term potentiation in hippocampus,” Prog. Brain Res., 118, 155–172 (1998).

    Article  PubMed  CAS  Google Scholar 

  22. Hegde, A. N., Haynes, K. A., Bach, S. V., and Beckelman, B. C., “Local ubiquitin-proteasome-mediated proteolysis and long-term synaptic plasticity,” Front. Mol. Neuroscience, 7, 95 (2014), doi: 10:3389/fnmol.2014.00096.

  23. Hernandez, A. I., Blace, N., Crary, J. F., et al., “Protein kinase M synthesis from a brain mRNA encoding an independent protein kinase C catalytic domain: implications for the molecular mechanism of memory,” J. Biol. Chem., 278, 40,305–40,316 (2003).

    Article  CAS  Google Scholar 

  24. Inda, M. C., Muravieva, E. V., and Alberini, C. M., “Memory retrieval and the passage of time: From reconsolidation and strengthening to extinction,” J. Neurosci., 31, 1635–1643 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Jacklet, J. W., “Nitric oxide signaling in invertebrates,” Invert. Neurosc., 3, 1–14 (1997).

    Article  CAS  Google Scholar 

  26. Jarome, T. J., Werner, C. T., Kwapis, J. L., and Helmstetter, F. J., “Activity dependent protein degradation is critical for the formation and stability of fear memory in the amygdala,” PLoS One, 6, (2011), doi: https://doi.org/10.1371/journal.pone.0024349.

  27. Katzoff, A., Ben-Gedalya, T., and Susswein, A. J., “Nitric oxide is necessary for multiple memory processes after learning that a food is inedible in Aplysia,” J. Neurosci., 22, 9581–9594 (2002).

    Article  PubMed  CAS  Google Scholar 

  28. Kelly, M. T., Crary, J. F., and Sacktor, T. C., “Regulation of protein kinase M synthesis by multiple kinases in long-term potentiation,” J. Neurosci., 27, 3439–3444 (2007).

    Article  PubMed  CAS  Google Scholar 

  29. Kwapis, J. L., Jarome, T. J., Gilmartin, M. R., and Helmstetter, F. J., “Intra-amygdala infusion of the protein kinase Mzeta inhibitor ZIP disrupts foreground context fear memory,” Neurobiol. Learn. Mem, 98, 148–153 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Lee, A. M., Kanter, B. R., Wang, D., et al., “Prkcz null mice show normal learning and memory,” Nature, 493, 416–419 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Lee, S.-H., Choi, J.-H., Lee, N., et al., “Synaptic protein degradation underlies destabilization of retrieved fear memory,” Science, 319, 1253–1256 (2008).

    Article  PubMed  CAS  Google Scholar 

  32. Ling, D. S. F., Benardo, L. S., Serrano, P. A., et al., “Protein kinase Mζ is necessary and sufficient for LTP maintenance,” Nat. Neurosci., 5, 295–296 (2002).

    Article  PubMed  CAS  Google Scholar 

  33. Litvin, O. O. and Anokhin, K. V., “The mechanisms of memory reorganization during the retrieval of acquired behavioral experience in chicks: the effects of protein synthesis blockade in the brain,” Zh. Vyssh. Nerv. Deyat., 49, No. 4, 554–65 (1999).

    CAS  Google Scholar 

  34. Mactutus, C. F., Riccio, D. C., and Ferek, J. M., “Retrograde amnesia for old (reactivated) memory: some anomalous characteristics,” Science, 204, 1319–1320 (1979).

    Article  PubMed  CAS  Google Scholar 

  35. Migues, P. V., Hardt, O., Wu, D. C., et al., “PKMζ maintains memories by regulating GluR2-dependent AMPA receptor trafficking,” Nat. Neurosci., 13, 630–634 (2010).

    Article  PubMed  CAS  Google Scholar 

  36. Misanin, J. R., Miller, R. R., and Lewis, D. J., “Retrograde amnesia produced by electroconvulsive shock after reactivation of a consolidated memory trace,” Science, 160, No. 3827, 554–555 (1968).

    Article  PubMed  CAS  Google Scholar 

  37. Muller, U., “The nitric oxide system in insects,” Prog. Neurobiol., 51, 363–381 (1997).

    Article  PubMed  CAS  Google Scholar 

  38. Nader, K., Schafe, G. E., and Le Doux, J. E., “Fear memories require protein synthesis in the amygdala for re-consolidation after retrieval,” Nature, 406, 722–726 (2000).

    Article  PubMed  CAS  Google Scholar 

  39. Nikitin, E. S., Balaban, P. M., and Kemenes, G., “Nonsynaptic plasticity underlies a compartmentalized increase in synaptic efficacy after classical conditioning,” Curr. Biol., 23, No. 7, 614–619 (2013).

    Article  PubMed  CAS  Google Scholar 

  40. Nishizuka, Y., “Protein kinase C and lipid signaling for sustained cellular responses,” FASEB J., 9, 484–496 (1995).

    Article  PubMed  CAS  Google Scholar 

  41. Pastalkova, E., Serrano, P., Pinkhasova, D., et al., “Storage of spatial information by the maintenance mechanism of LTP,” Science, 313, 1141–1144 (2006).

    Article  PubMed  CAS  Google Scholar 

  42. Pedreira, M. E. and Maldonado, H., “Protein synthesis subserves reconsolidation or extinction depending on reminder duration,” Neuron, 38, 863–869 (2003).

    Article  PubMed  CAS  Google Scholar 

  43. Ren, S.-Q., Yan, J.-Z., Zhang, X.-Y., et al., “PKCλ is critical in AMPA receptor phosphorylation and synaptic incorporation during LTP,” EMBO J., 32, 1365–1380 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Roberts, A. C. and Glanzman, D. L., “Learning in Aplysia: looking at synaptic plasticity from both sides,” Trends Neurosci., 26, 662–670 (2003).

    Article  PubMed  CAS  Google Scholar 

  45. Rose, S. P., “God’s organism? The chick as a model system for memory studies,” Learn. Mem., 7, 1–17 (2000).

    Article  PubMed  CAS  Google Scholar 

  46. Sacktor, T. C., “How does PKMzeta maintain long-term memory?” Nat. Rev. Neuroscience, 12, 9–15 (2011).

    Article  PubMed  CAS  Google Scholar 

  47. Sacktor, T. C., “Memory maintenance by PKMzeta – an evolutionary perspective,” Mol. Brain, 5, 31 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Sacktor, T. C., Osten, P., Valsamis, H., et al., “Persistent activation of the zeta isoform of protein kinase C in the maintenance of long-term potentiation,” Proc. Natl. Acad. Sci. USA, 90, 8342–8346 (1993).

    Article  PubMed  CAS  Google Scholar 

  49. Sara, S. J., “Strengthening the shaky trace through retrieval,” Nat. Rev. Neurosci., 1, 212–213 (2000).

    Article  PubMed  CAS  Google Scholar 

  50. Schweighofer, N. and Ferriol, G., “Diffusion of nitric oxide can facilitate cerebellar learning: A simulation study,” Proc. Natl. Acad. Sci. USA, 97, 10661–10665 (2000).

    Article  PubMed  CAS  Google Scholar 

  51. Shema, R., Hazvi, S., Sacktor, T. C., and Dudai, Y., “Boundary conditions for the maintenance of memory by PKM in neocortex,” Learn. Mem., 16, 122–128 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Shema, R., Sacktor, T. C., and Dudai, Y., “Rapid erasure of long-term memory associations in the cortex by an inhibitor of PKM,” Science, 317, 951–953 (2007).

    Article  PubMed  CAS  Google Scholar 

  53. Si, K., Lindquist, S., and Kandel, E. R., “A neuronal isoform of the Aplysia CPEB has prion-like properties,” Cell, 115, 879–891 (2003).

    Article  PubMed  CAS  Google Scholar 

  54. Suzuki, A., “Memory reconsolidation and extinction have distinct temporal and biochemical signatures,” J. Neurosci., 24, 4787–4795 (2004).

    Article  PubMed  CAS  Google Scholar 

  55. Tsokas, P., Hsieh, C., Yao, Y., et al., “Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice,” eLife, 5 (2016), doi: https://doi.org/10.7554/Elife.14846.

  56. Volk, L. J., Bachman, J. L., Johnson, R., et al., “PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory,” Nature, 493, 420–423 (2013).

    Article  PubMed  CAS  Google Scholar 

  57. Wass, C., Archer, T., Palsson, E., et al., “Phencyclidine affects memory in a nitric oxide-dependent manner: working and reference memory,” Behav. Brain Res., 174, 49–55 (2006).

    Article  PubMed  CAS  Google Scholar 

  58. Zyuzina, A. B. and Balaban, P. M., “Extinction and reconsolidation of memory,” Zh. Vyssh. Nerv. Deyat., 5, No. 5, 564–576 (2015).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P. M. Balaban.

Additional information

Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 67, No. 2, pp. 131–140, March–April, 2017.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Balaban, P.M. Molecular Mechanism of Memory Modification. Neurosci Behav Physi 48, 734–740 (2018). https://doi.org/10.1007/s11055-018-0624-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-018-0624-2

Keywords

Navigation