We studied the involvement of protein kinase Mζ (PKMζ) in the mechanisms of amnesia development within 10 days after disruption of conditioned food aversion memory with ZIP (a PKMζ inhibitor). Repeated training performed in 3 days after amnesia induction with ZIP, led to the formation of conditioned food aversion memory, but the number of combined presentations of food and reinforcer stimuli was lower than during the initial training. Repeated training performed in 10 days after amnesia induction also led to memory formation, but the number of combined presentations of the stimuli was similar to that during the initial training. It was hypothesized that at the early stages of ZIP-induced amnesia, residual memory trace can be restored and amplified during repeated training, which led to memory expression at the behavioral level. At the late stages of amnesia, this memory trace was completely erased and repeated training led to the formation of a new memory. Thus, PKMζ inhibition results in the relatively fast impairment of memory retrieval and induces long-term process of memory erasing.
Similar content being viewed by others
References
Solntseva SV, Kozyrev SA, Nikitin VP. Involvement of Mζ- Like Protein Kinase in the Mechanisms of Conditioned Food Aversion Memory Reconsolidation in the Helix lucorum. Bull. Exp. Biol. Med. 2015;159(2):192-196.
Balaban PM, Roshchin M, Timoshenko AKh, Zuzina AB, Lemak M, Ierusalimsky VN, Aseyev NA, Malyshev AY. Homolog of protein kinase Mζ maintains context aversive memory and underlying long-term facilitation in terrestrial snail Helix. Front. Cell. Neurosci. 2015;9:222. doi: https://doi.org/10.3389/fncel.2015.00222
Bougie JK, Lim T, Farah CA, Manjunath V, Nagakura I, Ferraro GB, Sossin WS. The atypical protein kinase C in Aplysia can form a protein kinase M by cleavage. J. Neurochem. 2009;109(4):1129-1143.
Cai D, Pearce K, Chen S, Glanzman DL. Protein kinase M maintains long-term sensitization and long-term facilitation in aplysia. J. Neurosci. 2011;31(17):6421-6431.
Chihabi K, Morielli AD, Green JT. Intracerebellar infusion of the protein kinase M zeta (PKMζ) inhibitor zeta-inhibitory peptide (ZIP) disrupts eyeblink classical conditioning. Behav. Neurosci. 2016;130(6):563-571.
Finnie PS, Nader K. The role of metaplasticity mechanisms in regulating memory destabilization and reconsolidation. Neurosci. Biobehav. Rev. 2012;36(7):1667-707.
Glanzman DL. PKM and the maintenance of memory. F1000 Biol. Rep. 2013;5. 4. doi: https://doi.org/10.3410/B5-4
Hu J, Adler K, Farah CA, Hastings MH, Sossin WS, Schacher S. Cell-Specific PKM Isoforms Contribute to the Maintenance of Different Forms of Persistent Long-Term Synaptic Plasticity. J. Neurosci. 2017;37(10):2746-2763.
Nikitin VP, Solntseva SV, Kozyrev SA, Nikitin PV, Shevelkin AV. NMDA or 5-HT receptor antagonists impair memory reconsolidation and induce various types of amnesia. Behav. Brain. Res. 2018;345:72-82.
Sacktor TC. How does PKMζ maintain long-term memory? Nat. Rev. Neurosci. 2011;12(1):9-15.
Serrano P, Friedman EL, Kenney J, Taubenfeld SM, Zimmerman JM, Hanna J, Alberini C, Kelley AE, Maren S, Rudy JW, Yin JC, Sacktor TC, Fenton AA. PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories. PLoS Biol. 2008;6(12):2698-2706. doi: https://doi.org/10.1371/journal.pbio.0060318
Yao Y, Shao C, Jothianandan D, Tcherepanov A, Shouval H, Sacktor T. C. Matching biochemical and functional efficacies confirm ZIP as a potent competitive inhibitor of PKMζ in neurons. Neuropharmacology. 2013;64:37-44.
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 167, No. 6, pp. 664-668, June, 2019
Rights and permissions
About this article
Cite this article
Nikitin, V.P., Solntseva, S.V. & Kozyrev, S.A. Changes in Amnesia Parameters over Time after Long-Term Memory Disruption with Protein Kinase Mζ Inhibitor. Bull Exp Biol Med 167, 711–715 (2019). https://doi.org/10.1007/s10517-019-04605-x
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-019-04605-x