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Science 331 (6021): 1207-1210

Copyright © 2011 by the American Association for the Advancement of Science

Enhancement of Consolidated Long-Term Memory by Overexpression of Protein Kinase M{zeta} in the Neocortex

Reut Shema,1 Sharon Haramati,1 Shiri Ron,1 Shoshi Hazvi,1 Alon Chen,1 Todd Charlton Sacktor,2 Yadin Dudai1,*

Abstract: Memories are more easily disrupted than improved. Many agents can impair memories during encoding and consolidation. In contrast, the armamentarium of potential memory enhancers is so far rather modest. Moreover, the effect of the latter appears to be limited to enhancing new memories during encoding and the initial period of cellular consolidation, which can last from a few minutes to hours after learning. Here, we report that overexpression in the rat neocortex of the protein kinase C isozyme protein kinase M{zeta} (PKM{zeta}) enhances long-term memory, whereas a dominant negative PKM{zeta} disrupts memory, even long after memory has been formed.

1 Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
2 Departments of Physiology, Pharmacology, and Neurology, The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA.

* To whom correspondence should be addressed. E-mail: yadin.dudai{at}

Cellular and subcellular localization of PKM{zeta}.
A. I. Hernandez, W. C. Oxberry, J. F. Crary, S. S. Mirra, and T. C. Sacktor (2013)
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GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories.
O. Hardt, K. Nader, and Y.-T. Wang (2013)
Phil Trans R Soc B 369, 20130141
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The roles of protein kinases in learning and memory.
K. P. Giese and K. Mizuno (2013)
Learn. Mem. 20, 540-552
   Abstract »    Full Text »    PDF »
An Increase in Synaptic NMDA Receptors in the Insular Cortex Contributes to Neuropathic Pain.
S. Qiu, T. Chen, K. Koga, Y.-y. Guo, H. Xu, Q. Song, J.-j. Wang, G. Descalzi, B.-K. Kaang, J.-h. Luo, et al. (2013)
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   Abstract »    Full Text »    PDF »
Increasing CRTC1 Function in the Dentate Gyrus during Memory Formation or Reactivation Increases Memory Strength without Compromising Memory Quality.
M. J. Sekeres, V. Mercaldo, B. Richards, D. Sargin, V. Mahadevan, M. A. Woodin, P. W. Frankland, and S. A. Josselyn (2012)
J. Neurosci. 32, 17857-17868
   Abstract »    Full Text »    PDF »
Overexpression of PKM{zeta} Alters Morphology and Function of Dendritic Spines in Cultured Cortical Neurons.
S. Ron, Y. Dudai, and M. Segal (2012)
Cereb Cortex 22, 2519-2528
   Abstract »    Full Text »    PDF »
Serotonin-Induced Cleavage of the Atypical Protein Kinase C Apl III in Aplysia.
J. K. Bougie, D. Cai, M. Hastings, C. A. Farah, S. Chen, X. Fan, P. K. McCamphill, D. L. Glanzman, and W. S. Sossin (2012)
J. Neurosci. 32, 14630-14640
   Abstract »    Full Text »    PDF »
Inhibition of Protein Kinase M{zeta} Disrupts the Stable Spatial Discharge of Hippocampal Place Cells in a Familiar Environment.
J. M. Barry, B. Rivard, S. E. Fox, A. A. Fenton, T. C. Sacktor, and R. U. Muller (2012)
J. Neurosci. 32, 13753-13762
   Abstract »    Full Text »    PDF »
Kainate receptor-mediated synaptic transmissions in the adult rodent insular cortex.
K. Koga, S.-E. Sim, T. Chen, L.-J. Wu, B.-K. Kaang, and M. Zhuo (2012)
J Neurophysiol 108, 1988-1998
   Abstract »    Full Text »    PDF »
Inhibiting PKM{zeta} reveals dorsal lateral and dorsal medial striatum store the different memories needed to support adaptive behavior.
W. M. Pauli, A. D. Clark, H. J. Guenther, R. C. O'Reilly, and J. W. Rudy (2012)
Learn. Mem. 19, 307-314
   Abstract »    Full Text »    PDF »
Synaptic Distributions of GluA2 and PKM{zeta} in the Monkey Dentate Gyrus and Their Relationships with Aging and Memory.
Y. Hara, M. Punsoni, F. Yuk, C. S. Park, W. G. M. Janssen, P. R. Rapp, and J. H. Morrison (2012)
J. Neurosci. 32, 7336-7344
   Abstract »    Full Text »    PDF »
Cellular Pharmacology of Protein Kinase M{zeta} (PKM{zeta}) Contrasts with Its in Vitro Profile: IMPLICATIONS FOR PKM{zeta} AS A MEDIATOR OF MEMORY.
A. X. Wu-Zhang, C. L. Schramm, S. Nabavi, R. Malinow, and A. C. Newton (2012)
J. Biol. Chem. 287, 12879-12885
   Abstract »    Full Text »    PDF »
Nerve growth factor enhances the excitability of rat sensory neurons through activation of the atypical protein kinase C isoform, PKM{zeta}.
Y. H. Zhang, J. Kays, K. E. Hodgdon, T. C. Sacktor, and G. D. Nicol (2012)
J Neurophysiol 107, 315-335
   Abstract »    Full Text »    PDF »
TrkB and Protein Kinase M {zeta} Regulate Synaptic Localization of PSD-95 in Developing Cortex.
A. Yoshii, Y. Murata, J. Kim, C. Zhang, K. M. Shokat, and M. Constantine-Paton (2011)
J. Neurosci. 31, 11894-11904
   Abstract »    Full Text »    PDF »
Intra-amygdala ZIP injections impair the memory of learned active avoidance responses and attenuate conditioned taste-aversion acquisition in rats.
F. Gamiz and M. Gallo (2011)
Learn. Mem. 18, 529-533
   Abstract »    Full Text »    PDF »
Spinal Protein Kinase M {zeta} Underlies the Maintenance Mechanism of Persistent Nociceptive Sensitization.
M. N. Asiedu, D. V. Tillu, O. K. Melemedjian, A. Shy, R. Sanoja, B. Bodell, S. Ghosh, F. Porreca, and T. J. Price (2011)
J. Neurosci. 31, 6646-6653
   Abstract »    Full Text »    PDF »

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