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This article is part of the supplement: Seventeenth Annual Computational Neuroscience Meeting: CNS*2008

Open Access Poster presentation

The self-sustained regulation of PKMζ activity during the maintenance of L-LTP

Naveed Aslam* and Harel Z Shouval

Author Affiliations

Department of Neurobiology and Anatomy. The University of Texas, Medical School at Houston, Texas, USA

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BMC Neuroscience 2008, 9(Suppl 1):P54  doi:10.1186/1471-2202-9-S1-P54

The electronic version of this article is the complete one and can be found online at:

Published:11 July 2008

© 2008 Aslam and Shouval; licensee BioMed Central Ltd.

Poster presentation

What could be the mechanism of enduring synaptic efficacies despite the fast turnover of proteins at synapses? The de-novo synthesis of plasticity related proteins may partially provide the answer. However, the newly synthesized proteins must be activated before they are functional which requires a persistent signal of second messenger. In contrast, to conventional kinases the PKMζ is an autonomous and constitutively active kinase, which does not require a second messenger for its sustained activity. Previous experimental results have shown that inhibiting PKMζ activity can effectively reverse the established L-LTP (3–5 hr in slices and 22 hrs in vivo) [1-3]. Here, we explore a question of what could be the mechanism to regulate the PKMζ activity during the maintenance of L-LTP. We propose a self-sustained regulation of PKMζ activity through another autonomously active kinase PDK1. Here, our specific instantiation of an activity regulation loop is the PKMζ-PDK1 molecular pair. The PDK1 regulates the PKMζ activity and its stability through a phosphorylation cycle [4]. We show that the PKMζ-PDK1 loop acts as a bistable switch. Our results imply that L-LTP induction should produce an increase in the total amount of PKMζ at active synapses, and this increase in PKMζ is maintained through activity regulation in the enduring phase of L-LTP (Fig 1). Our results also show that blocking the PKMζ activity in a dose dependent manner can effectively abolish the increase in total amount of PKMζ, (Fig 2) which is in consistent with previous experimental findings [1,2].

thumbnailFigure 1. Bistability characteristics of the PKMζ-PDK1 molecular pair.

thumbnailFigure 2. Blocking the PKMζ activity during maintenance of L-LTP.


  1. Pastalkova E, Serrano P, Pinkhasova D, Wallace E, Fenton AA, Sacktor TC: Storage of spatial information by the maintenance mechanism of LTP.

    Science 2006, 313:1141-1144. PubMed Abstract | Publisher Full Text OpenURL

  2. Ling DS, Benardo LS, Serrano PA, Blace N, Kelly MT, Crary JF, Sacktor TC: Protein kinase M is necessary and sufficient for LTP maintenance.

    Nat Neurosci 2002, 5:295-296. PubMed Abstract | Publisher Full Text OpenURL

  3. Bliss TV, Collingridge GL, Laroche S: Neuroscience. ZAP and ZIP, a story to forget.

    Science 2006, 313:1058-1059. PubMed Abstract | Publisher Full Text OpenURL

  4. Balendran A, Hare GR, Kieloch A, Williams MR, Alessi DR: Further evidence that 3-phosphoinositide-dependent protein kinase-1 (PDK1) is required for the stability and phosphorylation of protein kinase C (PKC) isoforms.

    FEBS Lett 2000, 484:217-223. PubMed Abstract | Publisher Full Text OpenURL